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MAIT cell-directed therapy of Mycobacterium tuberculosis infection.
- Source :
-
Mucosal immunology [Mucosal Immunol] 2021 Jan; Vol. 14 (1), pp. 199-208. Date of Electronic Publication: 2020 Aug 18. - Publication Year :
- 2021
-
Abstract
- Mucosal-associated invariant T (MAIT) cells are potential targets of vaccination and host-directed therapeutics for tuberculosis, but the role of MAIT cells during Mycobacterium tuberculosis (Mtb) infection in vivo is not well understood. Here we find that following Mtb infection MAIT cells mount minimal responses, and MAIT cell-deficient MR1 <superscript>-/-</superscript> mice display normal survival. Preinfection expansion of MAIT cells through 5-OP-RU vaccination fails to protect against subsequent Mtb challenge. In fact, 5-OP-RU vaccination delays Mtb-specific CD4 T cell priming in lung-draining lymph nodes, and conversely MR1 deficiency or blockade accelerates T cell priming. The MAIT cell-mediated delay in T cell priming is partly dependent on TGF-β. Surprisingly, 5-OP-RU treatment during chronic infection drives MAIT cell expansion and an IL-17A-dependent reduction in bacterial loads. Thus, during early infection MAIT cells directly contribute to the notoriously slow priming of CD4 T cells, but later during infection MAIT cell stimulation may be an effective host-directed therapy for tuberculosis.
- Subjects :
- Animals
Biomarkers
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes metabolism
Disease Models, Animal
Female
Host-Pathogen Interactions immunology
Immunophenotyping
Lymphocyte Activation genetics
Lymphocyte Activation immunology
Male
Mice
T-Cell Antigen Receptor Specificity
Transforming Growth Factor beta antagonists & inhibitors
Tuberculosis microbiology
Tuberculosis prevention & control
Adoptive Transfer methods
Mucosal-Associated Invariant T Cells immunology
Mycobacterium tuberculosis immunology
Tuberculosis immunology
Tuberculosis therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1935-3456
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Mucosal immunology
- Publication Type :
- Academic Journal
- Accession number :
- 32811991
- Full Text :
- https://doi.org/10.1038/s41385-020-0332-4