IL-10 Blocks Phagosome Maturation in Mycobacterium tuberculosis– Infected Human Macrophages
Abstract
Successful phagolysosomal maturation is an important innate immune response to intracellular infection. However, Mycobacterium tuberculosis (Mtb) can manipulate and inhibit this host response to ensure survival within its niche cell. We investigate the role of the anti-inflammatory cytokine IL-10 on Mtb-phagosome maturation. Blocking IL-10, which was secreted from Mtb-infected macrophages, allowed phagosome maturation to proceed. Macrophage cytokine gene expression profiles were not significantly altered by blocking IL-10 3 hours after infection with Mtb. We demonstrate that IL-10 can regulate this protective phenotype in phorbol myristate acetate (PMA)-treated THP-1 cells, monocyte-derived macrophages (MDMs), and human alveolar macrophages (AMs) infected with Mtb. The regulatory effect of endogenous IL-10 was evident in macrophages infected with virulent Mtb H37Rv, as well as in attenuated strains of mycobacteria. Unlike live Mtb, dead bacilli occupy a mature, acidic phagosome. However, the addition of IL-10 to cells infected with killed Mtb successfully inhibited the maturation of this compartment. Importantly, we demonstrate that the addition of IL-10 to MDMs results in enhanced mycobacterial survival and growth. Our results suggest that IL-10 exerts its effects on this early macrophage response in a partly signal transducer and activator of transcription 3 (STAT3)-dependent manner, and independent of mitogen activated protein kinase p38 (MAPKp38) and extracellular regulated kinase 1/2 (ERK1/2) activity. IL-10 is a feature of human tuberculous granuloma, and these new findings support the hypothesis that this cytokine can promote pathogen persistence by contributing to Mtb-phagosome maturation arrest in human macrophages.
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These data are consistent with IL-10 promoting pathogen persistence by contributing to Mtb-phagosome maturation.
“These data are consistent with IL-10 promoting pathogen persistence by contributing to Mtb- phagosome maturation (O’Leary et al., 2011).”
From Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the Warburg effect in LPS-activated macrophages (2015) · cites this paper as O’Leary et al., 2011
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- Authors
- O'Leary, S., O'Sullivan, M. P., & Keane, J.
- Affiliations
- Department of Clinical Medicine, Trinity College, Dublin, Ireland; and
- Trinity College Dublin (IE)
- ORCID
- Keane, Joseph
- Venue
- American Journal of Respiratory Cell and Molecular Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-07-01
- Volume
- 45
- Issue
- 1
- Pages
- 172-180
- ISSN
- 1044-1549 (ISSN-L)
- 1535-4989
- OpenAlex
- W2065362592
- Cited by
- 229
- References
- 59
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 11 · 2023: 12 · 2022: 16 · 2021: 16 · 2020: 13 · 2019: 17 · 2018: 21 · 2017: 19 · 2016: 15 · 2015: 12 · 2014: 23 · 2013: 14 · 2012: 12
- FWCI
- 7.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Respiratory Cell and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- IL-10, phagosome maturation, Mycobacterium tuberculosis, macrophages, phagolysosomes, innate immunity, STAT3 signaling, p38 MAPK, ERK1/2, mycobacterial survival, tuberculous granuloma, alveolar macrophages, monocyte-derived macrophages, THP-1 cells, attenuated mycobacteria, pathogen persistence
- MeSH terms
- Carcinogens, Cell Line, Granuloma, Humans, Macrophages, Mycobacterium tuberculosis, Phagosomes, Tetradecanoylphorbol Acetate, Tuberculosis, Interleukin-10, Mitogen-Activated Protein Kinase 1, p38 Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, STAT3 Transcription Factor
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