The DOI matches its Crossref record; 60 of the 61 references it cites were found in a registry or an index, and 1 are not checked yet; none of the 14 sources its claims cite is checked for support yet.
Heme induces innate immune memory
Open accessAbstract
Trained immunity defines long-lasting adaptive responses of innate immunity, mediated by transcriptional and epigenetic modifications of myeloid cells. Here, we report that labile heme, an alarmin released extracellularily upon tissue damage and hemolysis, induces trained immunity in human and murine primary cells and in mice. Heme-trainning in monocytes is associated with epigenetic and transcriptional profiles that overlap to some extent with those seen in β-glucan-training, the prototype agonist of trained immunity. In sharp contrast to β-glucan training however, heme-training relied on activation of the Syk/JNK-pathway. Heme training in mice was associated with long-lasting expansion of myeloid-biased progenitor cells as well as with altered chromatin accessibility in hematopoietic stem and progenitor cells. Finally, heme-induced training was protective against bacterial sepsis in mice. In conclusion, we reveal that heme, a bona fide alarmin, induces innate immune memory regulating host response to infection.
Checked 2026-11-11 · 1 reference not checked yet
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Labile heme acts as an alarmin that induces trained immunity in human and murine myeloid cells and in mice, with epigenetic and transcriptional overlap but a distinct Syk/JNK-dependent mechanism compared with β-glucan training. Heme training expands myeloid-biased hematopoietic progenitors and is protective in polymicrobial sepsis, yet worsens acute LPS endotoxemia.
Key findings
- Heme induced trained immunity in human and murine primary macrophages, increasing cytokine release upon secondary LPS or Pam3CSK4 challenge; training was also induced by iron-lacking protoporphyrin (PPIX) and was not prevented by N-acetyl cysteine.
- ChIP-seq showed that after heme exposure approximately 5% of all H3K27ac-marked regions increased versus untreated controls, with 497 peaks near 308 genes at 24 h; 98.6% of peaks occurred within 0.5 Mb of a gene TSS. RNA-seq at 24 h identified 201 genes commonly induced by heme and β-glucan, 140 heme-specific genes, and 346 β-glucan-specific genes.
- Heme training required Syk and JNK activation: Syk inhibition with R406 and JNK inhibition with SP600125 abolished training, while mTOR inhibition with rapamycin did not; Tlr4−/− BMDM were equally trained by heme.
- In mice, heme training increased myeloid-biased LT-HSCs (CD41+ LT-HSC) and MPP3 cells and decreased lymphoid-biased MPP4 cells, persisting 28 days after treatment; single-nuclei ATAC-seq of LSK cells showed altered chromatin accessibility. Heme-trained mice had reduced survival in LPS endotoxemia but faster weight recovery, higher temperature, and higher survival in polymicrobial sepsis.
Methods
- A 2-hit training model was used with human monocytes/macrophages and murine BMDM: first hit with heme (typically 50 µM) or β-glucan (1 µg/mL) for 24 h, washout and rest, then secondary challenge with LPS (10 ng/mL) or Pam3CSK4; cytokine release was measured by ELISA and LegendPlex.
- Epigenetic and transcriptional profiling included H3K27ac ChIP-seq, RNA-seq, ChIP-qPCR, Western blot, and single-nuclei ATAC-seq on sorted LSK cells; sequencing data were deposited under GEO accession GSE111003.
- Mouse experiments used C57Bl/6, Tlr4−/−, and Rag2−/− mice; heme was given at 2 mg/kg i.p., and LPS at 15 mg/kg one week later for survival, temperature, weight, clinical severity, and peritoneal flow cytometry. Statistical tests included log-rank, one-way/two-way ANOVA with Fisher’s LSD, and Student t-test.
Limitations
- Stated: how heme induces Syk phosphorylation independently of TLR4 is unknown; the authors speculate there may be no specific heme receptor and that Syk autophosphorylation could be enforced by heme–phospholipid interaction. It is also unclear how JNK signaling leads to histone modifications and which cofactors are involved.
- Stated: whether the observed effects rely on heme-driven modulation of BACH-1 remains to be established, and whether indirect cytokine effects mediate long-term myelopoiesis adaptation as proposed for β-glucan remains to be established. The analysis did not include H3K4me3 or H3K4me1 marks, although innate immune memory also involves histone methylation.
- Evident: the text is a preprint marked “not certified by peer review”; the single-nuclei ATAC-seq experiments used n = 2 mice per group at each time point, and the in vivo outcomes are context-dependent, with heme training deleterious in acute LPS endotoxemia but protective in polymicrobial sepsis.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
47 Own result · 13 Own interpretation · 7 No full text of the sources · 5 Own method · 4 Not checked yet · 1 Check pending
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Accordingly, heme-induced trained immunity was not prevented by the glutathione precursor N-Acetyl Cysteine (NAC) (Suppl.Fig.1)”
§ Heme induces innate immune memory > 5/37
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The deleterious effects of heme training on subsequent LPS-induced systemic inflammation persisted in Rag2 knock-out mice (Rag2 -/-) with a constitutive deficiency of mature B-and T-cells 45 as shown by significantly increased disease severity, significantly decreased temperature and decreased survival of heme-trained Rag2 -/-mice compared to control mice (Fig. 5g,h,i).”
§ Heme induces innate immune memory > 10/37
What the sources say
- Not checked — no full text of the sourcecites [45] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, a significant increase of mature neutrophils and monocyte is observed at this time point.”
§ Heme induces innate immune memory > 9/37
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Figure 2: Heme training evokes a specific transcriptional signature”
§ Heme induces innate immune memory > Dynamic H3K27ac
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our data show that primary human and murine myeloid cells can undergo heme-training resulting in specific changes of the expression of several hundred genes within 24 hours of exposure.”
§ Heme induces innate immune memory > CONCLUSION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, H3K27ac levels at genes related to adaptive immune regulation were downregulated by heme (Suppl.Fig.2).”
§ Heme induces innate immune memory > 6/37
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Figure 5: Heme training in vivo”
§ Heme induces innate immune memory > Dynamic H3K27ac
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Principial component analysis (PCA) plots based on the expression of common genes showed that heme and β-glucan exposed cells move faster along the differentiation trajectory (Fig. 2c)”
§ Heme induces innate immune memory > Heme induces distinct transcripts and common markers of innate immune memory
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We find that it can also be induced by protoporphyrin (PPIX), lacking iron (Suppl.Fig.1).”
§ Heme induces innate immune memory > 5/37
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Gene ontology (GO) analysis showed that heme exposure elevated H3K27ac signal near genes involved in wounding and stress”
§ Heme induces innate immune memory > 6/37
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 24
- Probably not a substantial claim. 8
- The quote only partly states this claim. 1
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“FACS analysis of immune cell subsets taken from peritoneum 6 hours after LPS application revealed no changes in total cell number, yet, numbers of classical monocytes and numbers of Mφ were significantly higher in heme-trained mice (Fig. 5e,f).”
§ Heme induces innate immune memory > 10/37
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Gene set enrichment analysis (GSEA) using the Molecular Signatures Database (MSigDB) (Fig. 2e) showed that common genes between heme and β-glucan induced pathways are involved in stress response, while the heme-specific response is related to inflammation and immune response and β-glucan induced pathways relate rather to metabolic processes.”
§ Heme induces innate immune memory > 7/37
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Strikingly, upon 28 days of heme treatment, several cell subpopulations were diminished, particularly MEP, and cells mostly concentrated on the HSC-MMP3-4 cluster (Fig. 4g,h; Suppl.Fig. 5,6).”
§ Heme induces innate immune memory > 9/37
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Training effects were specific to heme as i) different concentrations of LPS as a first stimulus resulted in immune tolerance”
§ Heme induces innate immune memory > 5/37
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Pathway analysis using GREAT 37 demonstrated that those pathways involved in cytokine-signaling and stress-response were up-regulated during heme training, in contrast to genes encoding metabolism and mitochondrial function in β-glucan training.”
§ Heme induces innate immune memory > 7/37
What the sources say
- Not checked yetcites [37] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The largest number of differentially expressed genes occurred at 24 hours after stimulation, with 201 genes commonly induced by heme and β-glucan, 140 specifically induced by heme and 346 specifically induced by β-glucan (Fig. 2a; Suppl.Table 3;4;5).”
§ Heme induces innate immune memory > Heme induces distinct transcripts and common markers of innate immune memory
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, we observed increased frequency of myeloid-biased LT-HSCs (CD41 + LT-HSC) 40 amongst the LT-HSC population as well as of myeloid-biased MPP3 cells (Flt3 -CD48 + CD150 -LSK) with a corresponding decrease of lymphoid-biased MPP4 cells (Flt3 + CD48 + CD150 -LSK) (Fig. 4a,b).”
§ Heme induces innate immune memory > 9/37
What the sources say
- Not checked — no full text of the sourcecites [40] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, when LPS was injected after 6 days, heme-trained mice displayed increased sickness behavior and increased temperature drops and significantly reduced survival when compared to control mice (Fig. 5b,c,d).”
§ Heme induces innate immune memory > 10/37
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ii) neither the application of ATP as a first hit nor heme as a second hit altered TNF release (Suppl.Fig.1).”
§ Heme induces innate immune memory > 5/37
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“while application of the JNK-Inhibitor SP600125 39 abolished JNK phosphorylation and heme-induced training (Fig. 3g;h).”
§ Heme induces innate immune memory > 8/37
What the sources say
- Not checked yetcites [39] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Heme application specifically induced transcription of heme/iron related genes HMOX1, FTH1, HRG1 but not of the iron exporter ferroportin (FPN1) (Suppl.Fig.3).”
§ Heme induces innate immune memory > 7/37
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Motif analysis of the gene promoter regions indicated that there is a β-glucan-specific signature (recognised by: USF and ELK1), hemespecific signature (e.g.NF-κB, BATF) and a common signature (AP-1, PPAR and MITF) (Fig. 2b).”
§ Heme induces innate immune memory > Heme induces distinct transcripts and common markers of innate immune memory
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also observed the expected upregulation of Dectin-1 target EGR2 by β-glucan exposure and upregulation of MITF and PPARG by both β-glucan and heme (Fig. 2d; Suppl.Fig.3).”
§ Heme induces innate immune memory > 7/37
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“JUN and FOSL were induced by heme, while ELK1 mRNA was induced exclusively by βglucan (Suppl.Fig.3).”
§ Heme induces innate immune memory > 7/37
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast to the endotoxemia model, heme-induced trained immunity was protective in polymicrobial sepsis as seen by a faster recovery of weight of heme pre-treated animals as well as a significantly higher temperature and a higher survival rate (Fig. 5j,k,l).”
§ Heme induces innate immune memory > 10/37
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The increased cytokine release was non-specific to TLR-4 signaling as activation of TLR1/2 signaling by the synthetic receptor agonist Pam3CSK4 used as the secondary challenge, also resulting in increased TNF-release (Fig. 1d).”
§ Heme induces innate immune memory > 5/37
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“H3K27ac dynamics are observed at both promoters and distal enhancer regions, with 98.6% of peaks occurring within 0.5Mb of a gene TSS (Suppl.Fig.2).”
§ Heme induces innate immune memory > 6/37
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The nuclei concentration was between 6,000 to 8,000 nuclei per µL.”
§ Heme induces innate immune memory > Nuclei isolation and single-nuclei ATAC library construction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The heme-dependent transcriptional repressor BACH-1 plays an essential role in the heme induced increase of myeloid cells, since it was shown that heme binding to BACH-1 causes a shift from erythropoiesis towards myelopoiesis in the bone marrow 52 , similar to observed in this study.”
§ Heme induces innate immune memory > 12/37
What the sources say
- Not checked — no full text of the sourcecites [52] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The samples were processed on the same day to avoid potential technical bias.”
§ Heme induces innate immune memory > 21/37
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The quote only partly states this claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Since the peak calling was performed separately, peaks do not overlap perfectly and might be treated as entirely different features.”
§ Heme induces innate immune memory > 25/37
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Heme imposes histone modifications and chromatin accessibility patterns and relies on signal transduction pathways involving the spleen tyrosine kinase mediated pathway, which is clearly distict from β-glucan-training.”
§ Heme induces innate immune memory > CONCLUSION
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Only samples which clearly showed training in TNF ELISA after normalization to protein were taken for the LegendPlex TM analysis.”
§ Heme induces innate immune memory > Cytokine measurements
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Cell purity was above 95%.”
§ Heme induces innate immune memory > 23/37
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The later have also been associated with β-glucan training and may therefore represent a pan-trained immunity signature.”
§ Heme induces innate immune memory > CONCLUSION
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In mice, innate immune memory induced by β-glucan or BCG was mostly protective 17,18,23,31 and is associated with increased myelopoiesis 25,26 which is also seen in heme induced innate immune memory.”
§ Heme induces innate immune memory > 12/37
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Here, we report that labile heme, an alarmin released extracellularily upon tissue damage and hemolysis, induces trained immunity in human and murine primary cells and in mice.”
- Also stated in: § 4/37 · boosted
“Here, we report that labile heme 9 induces potent trained immunity in vitro in human monocytes and Mφ, as well as in vivo in mice.”
§ Heme induces innate immune memory > Abstract
What the sources say
- Not checked — no full text of the sourcecites [9] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § 4/37 · boosted
In the paper
“Cells were filtered, keeping those with a TSS enrichment of at least five and more than 1,000 unique fragments.”
§ Heme induces innate immune memory > 25/37
What the sources say
- Not checked yetcites [58] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Mitroulis et al. showed that β-glucan training was associated with a specific expansion of myeloid-biased hematopoietic stem cells (HSC) 26 although HSC do not express the β-glucan receptor Dectin-1.”
§ Heme induces innate immune memory > 12/37
What the sources say
- Not checked yetcites [26] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We coclude that heme-induced trained immunity can be deleterious in acute inflammatory stress but improve the host defense against infections of sutle onset.”
§ Heme induces innate immune memory > 10/37
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The mouse endotoxemia and polymicrobial sepsis models reflect human acute inflammatory stress and infection sufficiently to support conclusions about host defense.
The paper relies on this without support.
The mouse endotoxemia and polymicrobial sepsis models reflect human acute inflammatory stress and infection sufficiently to support conclusions about host defense.
“We then assessed the effects of heme training in vivo using a mouse endotoxemia model (Fig. 5a).”
“we induced a smoldering bacterial sepsis.”
The paper relies on this without support.
Pharmacological inhibitors R406, SP600125, and rapamycin specifically inhibit Syk, JNK, and mTOR, respectively, at the concentrations used.
“Syk inhibition by R406 38 abolished heme-induced training (Fig. 3b;c).”
“application of the JNK-Inhibitor SP600125 39 abolished JNK phosphorylation and heme-induced training (Fig. 3g;h).”
“inhibition of mTOR activity by rapamycin did not abolish heme training”
The paper relies on this without support.
Changes in H3K27ac and chromatin accessibility measured at the assayed time points reflect functional epigenetic memory that mediates the long-lasting trained immunity phenotype.
“Heme imposes histone modifications and chromatin accessibility patterns”
“epigenetic alterations in HSPCs may contribute to the persistence of the heme-induced training effects.”
The paper relies on this without support.
Rag2-/- mice, lacking mature B and T cells, isolate innate immune-mediated effects.
“The deleterious effects of heme training on subsequent LPS-induced systemic inflammation persisted in Rag2 knock-out mice (Rag2 -/-) with a constitutive deficiency of mature B-and T-cells 45”
“This finding supports that heme-mediated trained immunity is predominantly mediated by effects on innate immune cells.”
Citations
Cites
Comprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453
Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394
GREAT improves functional interpretation of cis-regulatory regions
McLean, C. Y., Bristor, D., Hiller, M., Clarke, S. L., Schaar, B. T., Lowe, C. B., Wenger, A. M., & Bejerano, G. (2010) · Nature Biotechnology · doi:10.1038/nbt.1630 · Cited by 4,502
The Danger Model: A Renewed Sense of Self
Matzinger, P. (2002) · Science · doi:10.1126/science.1071059 · Cited by 4,205
Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051
Trained immunity: A program of innate immune memory in health and– disease
Netea, M. G., Joosten, L. A. B., Latz, E., Mills, K. H. G., Natoli, G., Stunnenberg, H. G., O’Neill, L. A. J., & Xavier, R. J. (2016) · Science · doi:10.1126/science.aaf1098 · Cited by 2,768
Self-citationSP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase
Bennett, B. L., Sasaki, D. T., Murray, B. W., O'Leary, E. C., Sakata, S. T., Xu, W., Leisten, J. C., Motiwala, A., Pierce, S., Satoh, Y., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251194298 · Cited by 2,558
mTOR- and HIF-1α–mediated aerobic glycolysis as metabolic basis for trained immunity
Cheng, S.-C., Quintin, J., Cramer, R. A., Shepardson, K. M., Saeed, S., Kumar, V., Giamarellos-Bourboulis, E. J., Martens, J. H. A., Rao, N. A., Aghajanirefah, A., et al. (2014) · Science · doi:10.1126/science.1250684 · Cited by 2,224
Self-citationRAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement
Shinkai, Y. (1992) · Cell · doi:10.1016/0092-8674(92)90029-c · Cited by 2,150
Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity
Saeed, S., Quintin, J., Kerstens, H. H. D., Rao, N. A., Aghajanirefah, A., Matarese, F., Cheng, S.-C., Ratter, J., Berentsen, K., van der Ent, M. A., et al. (2014) · Science · doi:10.1126/science.1251086 · Cited by 1,761
Self-citationKleinnijenhuis, J., Quintin, J., Preijers, F., Joosten, L. A. B., Ifrim, D. C., Saeed, S., Jacobs, C., van Loenhout, J., de Jong, D., Stunnenberg, H. G., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1202870109 · Cited by 1,728
Self-citationGene-specific control of inflammation by TLR-induced chromatin modifications
Foster, S. L., Hargreaves, D. C., & Medzhitov, R. (2007) · Nature · doi:10.1038/nature05836 · Cited by 1,344
Bouhlel, M. A., Derudas, B., Rigamonti, E., Dièvart, R., Brozek, J., Haulon, S., Zawadzki, C., Jude, B., Torpier, G., Marx, N., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.06.010 · Cited by 1,325
Quintin, J., Saeed, S., Martens, J. H. A., Giamarellos-Bourboulis, E. J., Ifrim, D. C., Logie, C., Jacobs, L., Jansen, T., Kullberg, B.-J., Wijmenga, C., et al. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.06.006 · Cited by 1,289
Self-citationBCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis
Kaufmann, E., Sanz, J., Dunn, J. L., Khan, N., Mendonça, L. E., Pacis, A., Tzelepis, F., Pernet, E., Dumaine, A., Grenier, J.-C., et al. (2018) · Cell · doi:10.1016/j.cell.2017.12.031 · Cited by 1,191
Heme oxygenase-1: unleashing the protective properties of heme
Otterbein, L. E., Soares, M. P., Yamashita, K., & Bach, F. H. (2003) · Trends in Immunology · doi:10.1016/s1471-4906(03)00181-9 · Cited by 1,166
Self-citationModulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity
Mitroulis, I., Ruppova, K., Wang, B., Chen, L.-S., Grzybek, M., Grinenko, T., Eugster, A., Troullinaki, M., Palladini, A., Kourtzelis, I., et al. (2018) · Cell · doi:10.1016/j.cell.2017.11.034 · Cited by 1,100
Self-citationTranscriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors
Paul, F., Arkin, Y., Giladi, A., Jaitin, D. A., Kenigsberg, E., Keren-Shaul, H., Winter, D., Lara-Astiaso, D., Gury, M., Weiner, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.11.013 · Cited by 1,082
Satpathy, A. T., Granja, J. M., Yost, K. E., Qi, Y., Meschi, F., McDermott, G. P., Olsen, B. N., Mumbach, M. R., Pierce, S. E., Corces, M. R., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0206-z · Cited by 980
Arts, R. J. W., Novakovic, B., ter Horst, R., Carvalho, A., Bekkering, S., Lachmandas, E., Rodrigues, F., Silvestre, R., Cheng, S.-C., Wang, S.-Y., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.10.008 · Cited by 930
Self-citationT cell– and B cell–independent adaptive immunity mediated by natural killer cells
O’Leary, J. G., Goodarzi, M., Drayton, D. L., & von Andrian, U. H. (2006) · Nature Immunology · doi:10.1038/ni1332 · Cited by 920
Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence
Gross, O., Poeck, H., Bscheider, M., Dostert, C., Hannesschläger, N., Endres, S., Hartmann, G., Tardivel, A., Schweighoffer, E., Tybulewicz, V., et al. (2009) · Nature · doi:10.1038/nature07965 · Cited by 819
A single-cell resolution map of mouse hematopoietic stem and progenitor cell differentiation
Nestorowa, S., Hamey, F. K., Pijuan Sala, B., Diamanti, E., Shepherd, M., Laurenti, E., Wilson, N. K., Kent, D. G., & Göttgens, B. (2016) · Blood · doi:10.1182/blood-2016-05-716480 · Cited by 768
Inflammatory memory sensitizes skin epithelial stem cells to tissue damage
Naik, S., Larsen, S. B., Gomez, N. C., Alaverdyan, K., Sendoel, A., Yuan, S., Polak, L., Kulukian, A., Chai, S., & Fuchs, E. (2017) · Nature · doi:10.1038/nature24271 · Cited by 745
β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance
Novakovic, B., Habibi, E., Wang, S.-Y., Arts, R. J. W., Davar, R., Megchelenbrink, W., Kim, B., Kuznetsova, T., Kox, M., Zwaag, J., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.034 · Cited by 712
Self-citationClonal analysis of lineage fate in native haematopoiesis
Rodriguez-Fraticelli, A. E., Wolock, S. L., Weinreb, C. S., Panero, R., Patel, S. H., Jankovic, M., Sun, J., Calogero, R. A., Klein, A. M., & Camargo, F. D. (2018) · Nature · doi:10.1038/nature25168 · Cited by 596
Characterization of Heme as Activator of Toll-like Receptor 4
Figueiredo, R. T., Fernandez, P. L., Mourao-Sa, D. S., Porto, B. N., Dutra, F. F., Alves, L. S., Oliveira, M. F., Oliveira, P. L., Graça-Souza, A. V., & Bozza, M. T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610737200 · Cited by 576
Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria
Pamplona, A., Ferreira, A., Balla, J., Jeney, V., Balla, G., Epiphanio, S., Chora, Â., Rodrigues, C. D., Gregoire, I. P., Cunha-Rodrigues, M., et al. (2007) · Nature Medicine · doi:10.1038/nm1586 · Cited by 560
Self-citationA Central Role for Free Heme in the Pathogenesis of Severe Sepsis
Larsen, R., Gozzelino, R., Jeney, V., Tokaji, L., Bozza, F. A., Japiassú, A. M., Bonaparte, D., Cavalcante, M. M., Chora, Â., Ferreira, A., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3001118 · Cited by 483
Self-citationBCG-induced trained immunity in NK cells: Role for non-specific protection to infection
Kleinnijenhuis, J., Quintin, J., Preijers, F., Joosten, L. A. B., Jacobs, C., Xavier, R. J., van der Meer, J. W. M., van Crevel, R., & Netea, M. G. (2014) · Clinical Immunology · doi:10.1016/j.clim.2014.10.005 · Cited by 473
Self-citationcisTopic: cis-regulatory topic modeling on single-cell ATAC-seq data
Bravo González-Blas, C., Minnoye, L., Papasokrati, D., Aibar, S., Hulselmans, G., Christiaens, V., Davie, K., Wouters, J., & Aerts, S. (2019) · Nature Methods · doi:10.1038/s41592-019-0367-1 · Cited by 456
Domínguez‐Andrés, J., Novakovic, B., Li, Y., Scicluna, B. P., Gresnigt, M. S., Arts, R. J. W., Oosting, M., Moorlag, S. J. C. F. M., Groh, L. A., Zwaag, J., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.09.003 · Cited by 403
Self-citationThe cis-Regulatory Atlas of the Mouse Immune System
Yoshida, H., Lareau, C. A., Ramírez, R. N., Rose, S. A., Maier, B. B., Wroblewska, A., Desland, F. A., Chudnovskiy, A., Mortha, A., Dominguez, C. X., et al. (2019) · Cell · doi:10.1016/j.cell.2018.12.036 · Cited by 385
Ifrim, D. C., Quintin, J., Joosten, L. A. B., Jacobs, C. W. M., Jansen, T., Jacobs, L., Gow, N. A. R., Williams, D. L., van der Meer, J. W. M., & Netea, M. G. (2014) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00688-13 · Cited by 373
Self-citationHeme on innate immunity and inflammation
Dutra, F. F., & Bozza, M. T. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00115 · Cited by 370
In Vitro Experimental Model of Trained Innate Immunity in Human Primary Monocytes
Bekkering, S., Blok, B. A., Joosten, L. A. B., Riksen, N. P., van Crevel, R., & Netea, M. G. (2016) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00349-16 · Cited by 364
Self-citationHemolysis-induced lethality involves inflammasome activation by heme
Dutra, F. F., Alves, L. S., Rodrigues, D., Fernandez, P. L., de Oliveira, R. B., Golenbock, D. T., Zamboni, D. S., & Bozza, M. T. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1405023111 · Cited by 353
CD41 expression marks myeloid-biased adult hematopoietic stem cells and increases with age
Gekas, C., & Graf, T. (2013) · Blood · doi:10.1182/blood-2012-09-457929 · Cited by 352
Sickle Hemoglobin Confers Tolerance to Plasmodium Infection
Ferreira, A., Marguti, I., Bechmann, I., Jeney, V., Chora, Â., Palha, N. R., Rebelo, S., Henri, A., Beuzard, Y., & Soares, M. P. (2011) · Cell · doi:10.1016/j.cell.2011.03.049 · Cited by 340
Self-citationTOLERANCE TO BACTERIAL PYROGENS
Beeson, P. B., & Roberts, W. T. T. A. O. E. (1947) · The Journal of Experimental Medicine · doi:10.1084/jem.86.1.29 · Cited by 339
Finn, A. V., Nakano, M., Polavarapu, R., Karmali, V., Saeed, O., Zhao, X., Yazdani, S. K., Otsuka, F., Davis, T., Habib, A., et al. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.10.852 · Cited by 330
DEL-1 promotes macrophage efferocytosis and clearance of inflammation
Kourtzelis, I., Li, X., Mitroulis, I., Grosser, D., Kajikawa, T., Wang, B., Grzybek, M., von Renesse, J., Czogalla, A., Troullinaki, M., et al. (2018) · Nature Immunology · doi:10.1038/s41590-018-0249-1 · Cited by 313
Self-citationFanucchi, S., Fok, E. T., Dalla, E., Shibayama, Y., Börner, K., Chang, E. Y., Stoychev, S., Imakaev, M., Grimm, D., Wang, K., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0298-2 · Cited by 303
Metabolic adaptation establishes disease tolerance to sepsis
Weis, S., Carlos, A. R., Moita, M. R., Singh, S., Blankenhaus, B., Cardoso, S., Larsen, R., Rebelo, S., Schäuble, S., Del Barrio, L., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.031 · Cited by 284 · cited 1×
“10 Weis, S. et al. Metabolic Adaptation Establishes Disease Tolerance to Sepsis. Cell 169, 1263-1275 e1214, doi:10.1016/j.cell.2017.05.031 (2017).”
BackgroundInfluentialSelf-citationTrained Immunity: An Ancient Way of Remembering
Netea, M. G., & van der Meer, J. W. M. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.02.003 · Cited by 259
Self-citationEvaluating Strategies to Normalise Biological Replicates of Western Blot Data
Degasperi, A., Birtwistle, M. R., Volinsky, N., Rauch, J., Kölch, W., & Kholodenko, B. Ν. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087293 · Cited by 236
A central role for free heme in the pathogenesis of severe malaria: the missing link?
Ferreira, A., Balla, J., Jeney, V., Balla, G., & Soares, M. P. (2008) · Journal of Molecular Medicine · doi:10.1007/s00109-008-0368-5 · Cited by 205
Self-citationA self-sustained loop of inflammation-driven inhibition of beige adipogenesis in obesity
Chung, K.-J., Chatzigeorgiou, A., Economopoulou, M., Garcia-Martin, R., Alexaki, V. I., Mitroulis, I., Nati, M., Gebler, J., Ziemssen, T., Goelz, S. E., et al. (2017) · Nature Immunology · doi:10.1038/ni.3728 · Cited by 175
Self-citationMolecular Mechanism of the Syk Activation Switch
Tsang, E. K., Giannetti, A. M., Shaw, D. E., Dinh, M. T., Tse, J. K. Y., Gandhi, S. C., Ho, H., Wang, S., Papp, E., & Bradshaw, J. M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806340200 · Cited by 164
Coupling Heme and Iron Metabolism via Ferritin H Chain
Gozzelino, R., & Soares, M. P. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5666 · Cited by 151
Self-citationRed alert: labile heme is an alarmin
Soares, M. P., & Bozza, M. T. (2016) · Current Opinion in Immunology · doi:10.1016/j.coi.2015.11.006 · Cited by 148
Self-citationImmunometabolic Crosstalk: An Ancestral Principle of Trained Immunity?
Penkov, S., Mitroulis, I., Hajishengallis, G., & Chavakis, T. (2018) · Trends in Immunology · doi:10.1016/j.it.2018.11.002 · Cited by 128
Self-citationGozzelino, R., Andrade, B. B., Larsen, R., Luz, N. F., Vanoaica, L., Seixas, E., Coutinho, A., Cardoso, S., Rebelo, S., Poli, M., et al. (2012) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) · Cited by 119
Self-citationInnate immune memory: Implications for host responses to damage‐associated molecular patterns
Crișan, T. O., Netea, M. G., & Joosten, L. A. B. (2016) · European Journal of Immunology · doi:10.1002/eji.201545497 · Cited by 118
Self-citationSecreted protein Del-1 regulates myelopoiesis in the hematopoietic stem cell niche
Mitroulis, I., Chen, L., Singh, R. P., Kourtzelis, I., Economopoulou, M., Kajikawa, T., Troullinaki, M., Ziogas, A., Ruppova, K., Hosur, K. B., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92571 · Cited by 101
Self-citationFernandez, P. L., Dutra, F. F., Alves, L., Figueiredo, R. T., Mourão-Sa, D., Fortes, G. B., Bergstrand, S., Lönn, D., Cevallos, R. R., Pereira, R. M. S., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.146076 · Cited by 95
Characterization of plasma labile heme in hemolytic conditions
Gouveia, Z., Carlos, A. R., Yuan, X., Aires‐da‐Silva, F., Stocker, R., Maghzal, G. J., Leal, S. S., Gomes, C. M., Todorovic, S., Iranzo, O., et al. (2017) · The FEBS Journal · doi:10.1111/febs.14192 · Cited by 70
Self-citationInfection perturbs Bach2- and Bach1-dependent erythroid lineage ‘choice’ to cause anemia
Kato, H., Itoh-Nakadai, A., Matsumoto, M., Ishii, Y., Watanabe-Matsui, M., Ikeda, M., Ebina-Shibuya, R., Sato, Y., Kobayashi, M., Nishizawa, H., et al. (2018) · Nature Immunology · doi:10.1038/s41590-018-0202-3 · Cited by 44
Labile heme impairs hepatic microcirculation and promotes hepatic injury
Englert, F. A., Seidel, R. A., Galler, K., Gouveia, Z. L., Soares, M. P., Neugebauer, U., Clemens, M. G., Sponholz, C., Heinemann, S. H., Pohnert, G., et al. (2019) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2019.108075 · Cited by 32
Self-citationA Distal Locus Element Mediates IFN-γ Priming of Lipopolysaccharide-Stimulated TNF Gene Expression
Chow, N. A., Jasenosky, L. D., & Goldfeld, A. E. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.11.011 · Cited by 26
Metabolic adaptation to tissue iron overload confers tolerance to malaria
Gozzelino, R., Andrade, B. B., Larsen, R., Luz, N. F., Vanoaica, L., Seixas, E., Coutinho, A., Cardoso, S., Rebelo, S., Poli, M., et al. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.10.011 · Cited by 3
Self-citation
Cited by
Sorted by citations
Sexual Dimorphism in Innate Immunity: The Role of Sex Hormones and Epigenetics
Shepherd, R., Cheung, A. S., Pang, K. C., Saffery, R., & Novakovic, B. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.604000 · Cited by 326
Self-citationPro-inflammatory Actions of Heme and Other Hemoglobin-Derived DAMPs
Bozza, M. T., & Jeney, V. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01323 · Cited by 214
Lysine methyltransferase G9a is an important modulator of trained immunity
Mourits, V. P., van Puffelen, J. H., Novakovic, B., Bruno, M., Ferreira, A. V., Arts, R. J. W., Groh, L. A., Crișan, T. O., Zwaag, J., Jentho, E., et al. (2021) · Clinical & Translational Immunology · doi:10.1002/cti2.1253 · Cited by 45
Self-citationChen, L., & Ozato, K. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.621333 · Cited by 41
Heme oxygenase-1 in protozoan infections: A tale of resistance and disease tolerance
Silva, R. C. M. C., Travassos, L. H., Paiva, C. N., & Bozza, M. T. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008599 · Cited by 31
Metadata
- Authors
- Jentho, E., Novakovic, B., Ruiz-Moreno, C., Kourtzelis, I., Martins, R., Chavakis, T., Soares, M. P., Kalafati, L., Guerra, J., Roestel, F., Bohm, P., Godmann, M., Grinenko, T., Eugster, A., Beretta, M., Joosten, L. A. B., Netea, M. G., Stunnenberg, H. G., Bauer, M., & Weis, S.
- Affiliations
- Jena University Hospital (DE)
- Radboud University Nijmegen (NL)
- Princess Máxima Center (NL)
- German Cancer Research Center (DE)
- Instituto Gulbenkian de Ciência (PT)
- Technische Universität Dresden (DE)
- Friedrich Schiller University Jena (DE)
- University of Bonn (DE)
- Corresponding author
- Weis, Sebastian
- ORCID
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2019-12-13
- OpenAlex
- W2995454016
- Semantic Scholar
- 965f2b755c4d514a0003c909b4203019551d6e17
- Cited by
- 10
- References
- 60
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 1 · 2021: 4 · 2020: 3
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (submittedVersion)
- Funders
- East Tennessee State University
- Deutsche Forschungsgemeinschaft (SFB-TRR 205, FOR1738, SFB1181, 01EO1502, Project A3, GRK1715, 1715/2)
- Bundesministerium für Bildung und Forschung (FOR 1738, 01EO1502)
- Universitätsklinikum Jena (01EO1502)
- Quillen College of Medicine, East Tennessee State University
- National Health and Medical Research Council (1173314)
- Center for Sepsis Control and Care (01EO1502)
- H2020 European Research Council (833247)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- heme, trained immunity, alarmins, monocytes, epigenetic modifications, chromatin accessibility, hematopoietic stem and progenitor cells, β-glucan, bacterial sepsis, myeloid progenitor cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
