Apoptotic Vesicles Crossprime CD8 T Cells and Protect against Tuberculosis
Open accessAbstract
CD8 T lymphocytes are important effectors in protective immunity against Mycobacterium tuberculosis. We recently characterized the detour pathway of CD8 T cell activation in tuberculosis mediated by apoptotic vesicles from infected cells that transport mycobacterial antigens to dendritic cells (DCs). Here we demonstrate that apoptotic vesicles from mycobacteria-infected macrophages stimulate CD8 T cells in vivo. Homing of DCs to draining lymph nodes was critically required for effective crosspriming. Subsequent fate of vesicle-associated antigens in recipient DCs was characterized by endosomal mechanisms predominating over proteasomal processing. In addition, vesicle processing depended on the presence of saposins to disintegrate apoptotic membranes. Apoptotic vesicles displayed potent adjuvant activity by stimulating through Toll-like receptors (TLR). Ultimately, vaccination with vesicles from infected cells induced protection against M. tuberculosis infection. Taken together, we propose the detour pathway to represent a genuine immunological mechanism mediating crosspriming of CD8 T cells in vivo and protection against 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 [137]
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- Authors
- Winau, F., Weber, S., Sad, S., de Diego, J., Hoops, S. L., Breiden, B., Sandhoff, K., Brinkmann, V., Kaufmann, S. H. E., & Schaible, U. E.
- Affiliations
- Max Planck Institute for Infection Biology (DE)
- Institute for Biological Sciences (CA)
- Corresponding author
- Winau, Florian
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 24
- Issue
- 1
- Pages
- 105-117
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2165948328
- Cited by
- 395
- References
- 53
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 19 · 2023: 8 · 2022: 16 · 2021: 13 · 2020: 14 · 2019: 12 · 2018: 14 · 2017: 15 · 2016: 15 · 2015: 17 · 2014: 31 · 2013: 25 · 2012: 22
- FWCI
- 23.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
- 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
- apoptotic vesicles, tuberculosis, Mycobacterium tuberculosis, dendritic cells, macrophages, antigen transport, saposins, Toll-like receptors, adjuvant effect, draining lymph nodes, protective immunity
- MeSH terms
- Adjuvants, Immunologic, Animals, BCG Vaccine, Dendritic Cells, Macrophages, Mycobacterium bovis, Endosomes, Tuberculosis, Vaccination, Apoptosis, CD8-Positive T-Lymphocytes, Cross-Priming, Saposins, Toll-Like Receptors, Mice
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