Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis
Abstract
Protective immunity against Mycobacterium tuberculosis involves major histocompatibility complex class I (MHC-I)- and CD1-restricted CD8 T cells, but the mechanisms underlying antigen delivery to antigen-presenting molecules remain enigmatic. Macrophages, the primary host cells for mycobacteria, are CD1-negative. Here we show that M. tuberculosis phagosomes are secluded from the cytosolic MHC-I processing pathway and that mycobacteria-infected cells lose their antigen-presenting capacity. We also show that mycobacteria induce apoptosis in macrophages, causing the release of apoptotic vesicles that carry mycobacterial antigens to uninfected antigen-presenting cells (APCs). Inhibition of apoptosis reduced transfer of antigens to bystander cells and activation of CD8 T cells. Uninfected dendritic cells, which engulfed extracellular vesicles, were indispensable for subsequent cross-presentation of antigens, through MHC-I and CD1b, to T cells from mycobacteria-sensitized donors. This new 'detour' pathway for presentation of antigens from a phagosome-contained pathogen shows the functional significance of infection-induced apoptosis in the activation of CD8 T cells specific for both protein and glycolipid antigens in tuberculosis.
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Apoptotic blebs from infected macrophages can promote cross presentation and protective T-cell immunity.
“As reported previously, apoptotic blebs from infected MΦs can also promote cross presentation and protective T-cell immunity (137, 157).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [157]
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- Authors
- Schaible, U. E., Winau, F., Sieling, P. A., Fischer, K., Collins, H. L., Hagens, K., Modlin, R. L., Brinkmann, V., & Kaufmann, S. H. E.
- Affiliations
- Max Planck Society (DE)
- University of California, Los Angeles (US)
- Corresponding author
- Schaible, Ulrich E
- ORCID
- Venue
- Nature Medicine
- Published
- 2003-07-20
- Volume
- 9
- Issue
- 8
- Pages
- 1039-1046
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2008626549
- Cited by
- 546
- References
- 41
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 10 · 2023: 11 · 2022: 22 · 2021: 15 · 2020: 8 · 2019: 12 · 2018: 16 · 2017: 28 · 2016: 24 · 2015: 22 · 2014: 39 · 2013: 23 · 2012: 28
- FWCI
- 22.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB421)
- Bundesministerium für Bildung und Forschung
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- tuberculosis, Mycobacterium tuberculosis, apoptosis, antigen presentation, MHC class I, CD1b, CD8+ T cells, cross-presentation, dendritic cells, macrophages, phagosome, extracellular vesicles, glycolipid antigens, protective immunity
- MeSH terms
- Animals, Antigen-Presenting Cells, Antigens, Bacterial, Genes, MHC Class I, Humans, Listeria monocytogenes, Lymphocyte Activation, Macrophages, Mycobacterium tuberculosis, Phagosomes, Tuberculosis, Histocompatibility Antigens Class I, Apoptosis, Antigen Presentation, CD8-Positive T-Lymphocytes, Antigens, CD1, Mice
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