Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection
Open accessAbstract
Lymphocytes and neutrophils are rapidly depleted by systemic infection. Progenitor cells of the haematopoietic system, such as common myeloid progenitors and common lymphoid progenitors, increase the production of immune cells to restore and maintain homeostasis during chronic infection, but the contribution of haematopoietic stem cells (HSCs) to this process is largely unknown. Here we show, using an in vivo mouse model of Mycobacterium avium infection, that an increased proportion of long-term repopulating HSCs proliferate during M. avium infection, and that this response requires interferon-gamma (IFN-gamma) but not interferon-alpha (IFN-alpha) signalling. Thus, the haematopoietic response to chronic bacterial infection involves the activation not only of intermediate blood progenitors but of long-term repopulating HSCs as well. IFN-gamma is sufficient to promote long-term repopulating HSC proliferation in vivo; furthermore, HSCs from IFN-gamma-deficient mice have a lower proliferative rate, indicating that baseline IFN-gamma tone regulates HSC activity. These findings implicate IFN-gamma both as a regulator of HSCs during homeostasis and under conditions of infectious stress. Our studies contribute to a deeper understanding of haematological responses in patients with chronic infections such as HIV/AIDS or tuberculosis.
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Titration of doxycycline concentration in chow identified a dose that approximated serum levels of IFNγ in mice infected with the Mycobacterium avium pathogen.
“Titration of doxycycline concentration in chow (Supplementary Fig. S4A) identified a dose that approximated serum levels of IFNγ in mice infected with the Mycobacterium avium pathogen (29).”
From <i>Txnip</i> Enhances Fitness of <i>Dnmt3a</i> -Mutant Hematopoietic Stem Cells via <i>p21</i> (2022) · cites this paper as [29]
The passage on IFNγ during M. avium infection (labelled Abstract in our copy; page unavailable) reports increased IFNγ in infected mice’s bone marrow and refers to previous findings in serum. It gives no serum concentration against which a doxycycline dose could be compared. The chow titration is attributed to the citing paper’s own supplementary figure, not to this source. (LLM, conf=0.81)
Experimental — accuracy not yet measuredIFN-g is produced during acute infections and leads to activation and proliferation of otherwise quiescent HSCs to immunologically fight pathogens.
“IFN-g, a prominent type II interferon, is produced during acute infections and leads to an activation and proliferation of otherwise quiescent HSCs to immunologically fight pathogens.20”
From Inflammatory bone marrow microenvironment (2019) · cites this paper as [20]
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- Authors
- Baldridge, M. T., King, K. Y., Boles, N. C., Weksberg, D. C., & Goodell, M. A.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Goodell, Margaret A.
- Venue
- Nature
- Published
- 2010-06
- Volume
- 465
- Issue
- 7299
- Pages
- 793-797
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2935898
- OpenAlex
- W2072411272
- Cited by
- 877
- References
- 32
- Citations by year
- 2026: 31 · 2025: 52 · 2024: 56 · 2023: 67 · 2022: 67 · 2021: 72 · 2020: 61 · 2019: 49 · 2018: 60 · 2017: 60 · 2016: 68 · 2015: 48 · 2014: 56 · 2013: 50 · 2012: 36
- FWCI
- 26.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (K08HL098898, U54HL081007, R01HL096360, T32HL092332)
- National Cancer Institute (P50CA126752)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058192, F30DK082107)
- National Institute of Biomedical Imaging and Bioengineering (R01EB005173)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- hematopoietic stem cells, interferon-gamma, chronic bacterial infection, Mycobacterium avium, HSC proliferation, HSC quiescence, hepatic stellate cell activation, interferon-alpha, bone marrow homeostasis, immune cell depletion, HIV/AIDS, tuberculosis, bone marrow transplantation
- MeSH terms
- Animals, Cell Count, Chronic Disease, Hematopoietic Stem Cells, Homeostasis, Interferon-gamma, Mice, Inbred C57BL, Mycobacterium avium, Tuberculosis, Signal Transduction, Bone Marrow Transplantation, Interferon-alpha, Multipotent Stem Cells, Cell Proliferation, Mice
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