Gr1intCD11b+ Myeloid-Derived Suppressor Cells in Mycobacterium tuberculosis Infection
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BACKGROUND: Tuberculosis is one of the world's leading killers, stealing 1.4 million lives and causing 8.7 million new and relapsed infections in 2011. The only vaccine against tuberculosis is BCG which demonstrates variable efficacy in adults worldwide. Human infection with Mycobacterium tuberculosis results in the influx of inflammatory cells to the lung in an attempt to wall off bacilli by forming a granuloma. Gr1(int)CD11b(+) cells are called myeloid-derived suppressor cells (MDSC) and play a major role in regulation of inflammation in many pathological conditions. Although MDSC have been described primarily in cancer their function in tuberculosis remains unknown. During M. tuberculosis infection it is crucial to understand the function of cells involved in the regulation of inflammation during granuloma formation. Understanding their relative impact on the bacilli and other cellular phenotypes is necessary for future vaccine and drug design. METHODOLOGY/PRINCIPAL FINDINGS: We compared the bacterial burden, lung pathology and Gr1(int)CD11b(+) myeloid-derived suppressor cell immune responses in M. tuberculosis infected NOS2-/-, RAG-/-, C3HeB/FeJ and C57/BL6 mice. Gr-1(+) cells could be found on the edges of necrotic lung lesions in NOS2-/-, RAG-/-, and C3HeB/FeJ, but were absent in wild-type mice. Both populations of Gr1(+)CD11b(+) cells expressed high levels of arginase-1, and IL-17, additional markers of myeloid derived suppressor cells. We then sorted the Gr1(hi) and Gr1(int) populations from M. tuberculosis infected NOS-/- mice and placed the sorted both Gr1(int) populations at different ratios with naïve or M. tuberculosis infected splenocytes and evaluated their ability to induce activation and proliferation of CD4+T cells. Our results showed that both Gr1(hi) and Gr1(int) cells were able to induce activation and proliferation of CD4+ T cells. However this response was reduced as the ratio of CD4(+) T to Gr1(+) cells increased. Our results illustrate a yet unrecognized interplay between Gr1(+) cells and CD4(+) T cells in tuberculosis.
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MDSC of the GR1intermediate/CD11b+ phenotype expressing IL-17 and arg1 accumulate at the rim of M. tuberculosis-induced lung granulomas, especially in the absence of NOS2, where they may be protective.
“MDSC, as these cells are termed today, of the GR1intermediate/CD11b+ phenotype expressing IL-17 and arg1 accumulate at the rim of M. tuberculosis-induced lung granulomas, especially in the absence of NOS2, where they may be protective (111).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [111]
Different macrophage populations are important to keep the tight balance between exacerbated pathology and control of bacterial growth.
“These studies indicate that different MO populations are important to keep the tight balance between exacerbated pathology and control of bacterial growth.”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [111]
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- Authors
- Obregón-Henao, A., Henao-Tamayo, M., Orme, I. M., & Ordway, D. J.
- Affiliations
- Colorado State University (US)
- Corresponding author
- Ordway, Diane J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-11-01
- Volume
- 8
- Issue
- 11
- Pages
- e80669
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3815237
- OpenAlex
- W1976566701
- Cited by
- 74
- References
- 54
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 8 · 2017: 9 · 2016: 9 · 2015: 12 · 2014: 9 · 2012: 1
- FWCI
- 7.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (1dp2od006450-01)
- National Institute of Allergy and Infectious Diseases (R21AI081959, AI081959)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- myeloid-derived suppressor cells, Mycobacterium tuberculosis, tuberculosis, granuloma formation, arginase-1, IL-17, CD4+ T cell activation, T cell proliferation, RAG-deficient mice, inflammation regulation, bacterial load
- MeSH terms
- Animals, Mycobacterium Infections, Mycobacterium tuberculosis, Mice, Knockout, Receptors, Chemokine, Myeloid Cells, CD11b Antigen, Mice, Nitric Oxide Synthase Type II
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