Sensing of the microbiota by NOD1 in mesenchymal stromal cells regulates murine hematopoiesis
Open accessAbstract
The microbiota is known to influence the generation of hematopoietic progenitors, although the pathways underlying this process are still poorly understood. NOD1 and NOD2 are intracellular sensors for both Gram-positive and Gram-negative bacteria, but their role in steady-state hematopoiesis has never been characterized. We observed that stimulation with NOD1 or NOD2 ligand had no effect on the survival/proliferation of hematopoietic precursors. Nonetheless, NOD1, but not NOD2, ligand induced expression of multiple hematopoietic cytokines (interleukin-7 [IL-7], Flt3L, stem cell factor [SCF], ThPO, and IL-6) from bone marrow mesenchymal stromal cells (MSCs) in vitro. Moreover, in vivo administration of NOD1 ligand to germ-free mice restored the numbers of hematopoietic stem cells and precursors in bone marrow as well as serum concentrations of IL-7, Flt3L, SCF, and ThPO to the levels displayed by specific pathogen-free control animals. Based on these findings, we propose that NOD1 signaling in MSCs serves as an important pathway underlying the requirement for microbiota in the maintenance of steady-state hematopoiesis. This function is distinct from that triggered by lipopolysaccharide in both its broad effects on multiple progenitors and specific targeting of MSCs as cytokine producing intermediates.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Nod1 signaling in mesenchymal stromal cells regulates hematopoiesis.
“Nod1 signaling in mesenchymal stromal cells regulates hematopoiesis (Iwamura et al., 2017).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Iwamura et al., 2017
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43
Maslowski, K. M., Vieira, A. T., Ng, A., Kranich, J., Sierro, F., Yu, D., Schilter, H. C., Rolph, M. S., Mackay, F., Artis, D., et al. (2009) · Nature · doi:10.1038/nature08530 · Cited by 3,241 · see citing works
An Immunomodulatory Molecule of Symbiotic Bacteria Directs Maturation of the Host Immune System
Mazmanian, S. K., Liu, C. H., Tzianabos, A. O., & Kasper, D. L. (2005) · Cell · doi:10.1016/j.cell.2005.05.007 · Cited by 2,910 · see citing works
Gut Microbiota Metabolism of Dietary Fiber Influences Allergic Airway Disease and Hematopoiesis
Trompette, A., Gollwitzer, E. S., Yadava, K., Sichelstiel, A. K., Sprenger, N., Ngom-Bru, C., Blanchard, C., Junt, T., Nicod, L. P., Harris, N. L., et al. (2014) · Nature Medicine · doi:10.1038/nm.3444 · Cited by 2,862 · see citing works
The bone marrow niche for haematopoietic stem cells
Morrison, S. J., & Scadden, D. T. (2014) · Nature · doi:10.1038/nature12984 · Cited by 2,451 · see citing works
Nod1 Detects a Unique Muropeptide from Gram-Negative Bacterial Peptidoglycan
Girardin, S. E., Boneca, I. G., Carneiro, L. A. M., Antignac, A., Jéhanno, M., Viala, J., Tedin, K., Taha, M., Labigne-Roussel, A., Zäthringer, U., et al. (2003) · Science · doi:10.1126/science.1084677 · Cited by 1,574 · see citing works
Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity
Clarke, T. B., Davis, K. M., Lysenko, E. S., Zhou, A. Y., Yu, Y., & Weiser, J. N. (2010) · Nature Medicine · doi:10.1038/nm.2087 · Cited by 1,154 · see citing works
Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection
Baldridge, M. T., King, K. Y., Boles, N. C., Weksberg, D. C., & Goodell, M. A. (2010) · Nature · doi:10.1038/nature09135 · Cited by 877 · see citing works
Toll-like Receptors on Hematopoietic Progenitor Cells Stimulate Innate Immune System Replenishment
Nagai, Y., Garrett, K. P., Ohta, S., Bahrun, U., Kouro, T., Akira, S., Takatsu, K., & Kincade, P. W. (2006) · Immunity · doi:10.1016/j.immuni.2006.04.008 · Cited by 833 · see citing works
NOD1 and NOD2: Signaling, Host Defense, and Inflammatory Disease
Caruso, R., Warner, N., Inohara, N., & Núñez, G. (2014) · Immunity · doi:10.1016/j.immuni.2014.12.010 · Cited by 830 · see citing works
Gut Microbiota Promote Hematopoiesis to Control Bacterial Infection
Khosravi, A., Yáñez, A., Price, J. G., Chow, A. T., Mérad, M., Goodridge, H. S., & Mazmanian, S. K. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.02.006 · Cited by 651 · see citing works
Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response
King, K. Y., & Goodell, M. A. (2011) · Nature reviews. Immunology · doi:10.1038/nri3062 · Cited by 565 · see citing works
Shi, C., Jia, T., Méndez‐Ferrer, S., Hohl, T. M., Serbina, N. V., Lipuma, L., Leiner, I. M., Li, M. O., Frenette, P. S., & Pamer, E. G. (2011) · Immunity · doi:10.1016/j.immuni.2011.02.016 · Cited by 508 · see citing works
Regulation of hematopoietic stem cells by bone marrow stromal cells
Anthony, B. A., & Link, D. C. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.10.002 · Cited by 301 · see citing works
Dynamic variation in cycling of hematopoietic stem cells in steady state and inflammation
Takizawa, H., Regoes, R. R., Boddupalli, C. S., Bonhoeffer, S., & Manz, M. G. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20101643 · Cited by 283 · see citing works
Microbiota-Derived Compounds Drive Steady-State Granulopoiesis via MyD88/TICAM Signaling
Balmer, M. L., Schürch, C. M., Saito, Y., Geuking, M. B., Li, H., Miguelangel Cuenca, V., Kovtonyuk, L. V., McCoy, K. D., Hapfelmeier, S., Ochsenbein, A. F., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400762 · Cited by 274 · see citing works
Role of Nod2 in the Response of Macrophages to Toll-Like Receptor Agonists
Pauleau, A., & Murray, P. J. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.21.7531-7539.2003 · Cited by 261 · see citing works
Schürch, C. M., Riether, C., & Ochsenbein, A. F. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.01.002 · Cited by 213 · see citing works
Scumpia, P. O., Kelly‐Scumpia, K. M., Delano, M. J., Weinstein, J. S., Cuenca, A. G., Al‐Quran, S. Z., Bovio, I. M., Akira, S., Kumagai, Y., & Moldawer, L. L. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903652 · Cited by 129 · see citing works
The human microbiome in hematopoiesis and hematologic disorders
Manzo, V. E., & Bhatt, A. S. (2015) · Blood · doi:10.1182/blood-2015-04-574392 · Cited by 93 · see citing works
García‐García, A., de Castillejo, C. L. F., & Méndez‐Ferrer, S. (2015) · Immunology Letters · doi:10.1016/j.imlet.2015.06.020 · Cited by 59 · see citing works
Ziegler, P., Boettcher, S., Takizawa, H., Manz, M. G., & Brümmendorf, T. H. (2015) · Annals of Hematology · doi:10.1007/s00277-015-2550-5 · Cited by 40 · see citing works
Taki, M., Tsuboi, I., Harada, T., Naito, M., Hara, H., Inoue, T., & Aizawa, S. (2014) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b14-00279 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Homeostatic Immunity and the Microbiota
Belkaid, Y., & Harrison, O. J. (2017) · Immunity · doi:10.1016/j.immuni.2017.04.008 · Cited by 1,261 · see citing works
Self-citationMicrobes, Metabolites, and the Gut-Lung Axis
Dang, A. T., & Marsland, B. J. (2019) · Mucosal Immunology · doi:10.1038/s41385-019-0160-6 · Cited by 1,028 · see citing works
Kennedy, E. A., King, K. Y., & Baldridge, M. T. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01534 · Cited by 602 · see citing works
The microbiota protects against respiratory infection via GM-CSF signaling
Brown, R. L., Sequeira, R. P., & Clarke, T. B. (2017) · Nature Communications · doi:10.1038/s41467-017-01803-x · Cited by 378 · see citing works
Zeng, X., Li, X., Li, X., Wei, C., Shi, C., Hu, K., Kong, D., Luo, Q., Xu, Y., Shan, W., et al. (2023) · Blood · doi:10.1182/blood.2022017514 · Cited by 157 · see citing works
Inflammatory signaling regulates hematopoietic stem and progenitor cell development and homeostasis
Collins, A., Mitchell, C. A., & Passegué, E. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20201545 · Cited by 111 · see citing works
Zhang, Q., Pan, Y., Zeng, B., Zheng, X., Wang, H., Shen, X., Li, H., Jiang, Q., Zhao, J., Meng, Z.-X., et al. (2019) · Cell Research · doi:10.1038/s41422-019-0190-3 · Cited by 73 · see citing works
How microbiota improve immunotherapy
Ansaldo, E., & Belkaid, Y. (2021) · Science · doi:10.1126/science.abl3656 · Cited by 54 · see citing works
Self-citationBone marrow immune cells respond to fluctuating nutritional stress to constrain weight regain
Zhou, H.-Y., Feng, X., Wang, L.-W., Zhou, R., Sun, H., Chen, X., Lu, R.-B., Huang, Y., Guo, Q., & Luo, X.-H. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.08.009 · Cited by 30 · see citing works
Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells
Xiang, C., Chen, P., Zhang, Q., Li, Y., Pan, Y., Xie, W., Sun, J., & Liu, Z. (2021) · iScience · doi:10.1016/j.isci.2021.102849 · Cited by 15 · see citing works
- Authors
- Iwamura, C., Bouladoux, N., Belkaid, Y., Sher, A., & Jankovic, D.
- Affiliations
- National Institute of Allergy and Infectious Diseases (US)
- National Institutes of Health (US)
- Corresponding author
- Sher, Alan
- Jankovic, Dragana
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2017-01-12
- Volume
- 129
- Issue
- 2
- Pages
- 171-176
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC5234217
- OpenAlex
- W2543679265
- Cited by
- 137
- References
- 22
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 24 · 2023: 14 · 2022: 15 · 2021: 23 · 2020: 15 · 2019: 14 · 2018: 12 · 2017: 7
- FWCI
- 10.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- McGill University
- Uehara Memorial Foundation
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- NOD1, NOD2, gut microbiota, mesenchymal stem cells, hematopoiesis, hematopoietic stem cells, hematopoietic progenitor cells, germ-free mice, cytokine production, IL-7, Flt3L, stem cell factor, interleukin-6, innate immune recognition, bone marrow
- MeSH terms
- Animals, Bone Marrow Cells, Cell Separation, Cells, Cultured, Flow Cytometry, Germ-Free Life, Hematopoiesis, Mice, Inbred C57BL, Polymerase Chain Reaction, Mice, Knockout, Mice, Nod1 Signaling Adaptor Protein, Mesenchymal Stem Cells, Microbiota
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.
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
