Mucosal-associated invariant T-cell activation and accumulation after in vivo infection depends on microbial riboflavin synthesis and co-stimulatory signal

Chen, Z., Wang, H., D'Souza, C., Sun, S., Kostenko, L., Eckle, S. B. G, Meehan, B. S., Jackson, D.C., Strugnell, R. A., Cao, H., Wang, N., Fairlie, David, Liu, L., Godfrey, D. I., Rossjohn, J., McCluskey, J. and Corbett, A. J. (2017) Mucosal-associated invariant T-cell activation and accumulation after in vivo infection depends on microbial riboflavin synthesis and co-stimulatory signal. Mucosal Immunology, 10 1: 58-68. doi:10.1038/mi.2016.39

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Author Chen, Z.
Wang, H.
D'Souza, C.
Sun, S.
Kostenko, L.
Eckle, S. B. G
Meehan, B. S.
Jackson, D.C.
Strugnell, R. A.
Cao, H.
Wang, N.
Fairlie, David
Liu, L.
Godfrey, D. I.
Rossjohn, J.
McCluskey, J.
Corbett, A. J.
Title Mucosal-associated invariant T-cell activation and accumulation after in vivo infection depends on microbial riboflavin synthesis and co-stimulatory signal
Formatted title
Mucosal-associated invariant T-cell activation and accumulation after in vivo infection depends on microbial riboflavin synthesis and co-stimulatory signal
Journal name Mucosal Immunology   Check publisher's open access policy
ISSN 1933-0219
1935-3456
Publication date 2017-01-01
Year available 2016
Sub-type Article (original research)
DOI 10.1038/mi.2016.39
Open Access Status File (Author Post-print)
Volume 10
Issue 1
Start page 58
End page 68
Total pages 11
Place of publication New York, United States
Publisher Nature Publishing Group
Language eng
Abstract Despite recent breakthroughs in identifying mucosal-associated invariant T (MAIT) cell antigens (Ags), the precise requirements for in vivo MAIT cell responses to infection remain unclear. Using major histocompatibility complex-related protein 1 (MR1) tetramers, the MAIT cell response was investigated in a model of bacterial lung infection employing riboflavin gene-competent and -deficient bacteria. MAIT cells were rapidly enriched in the lungs of C57BL/6 mice infected with Salmonella Typhimurium, comprising up to 50% of αβ-T cells after 1 week. MAIT cell accumulation was MR1-dependent, required Ag derived from the microbial riboflavin synthesis pathway, and did not occur in response to synthetic Ag, unless accompanied by a Toll-like receptor agonist or by co-infection with riboflavin pathway-deficient S. Typhimurium. The MAIT cell response was associated with their long-term accumulation in the lungs, draining lymph nodes and spleen. Lung MAIT cells from infected mice displayed an activated/memory phenotype, and most expressed the transcription factor retinoic acid-related orphan receptor γt. T-bet expression increased following infection. The majority produced interleukin-17 while smaller subsets produced interferon-γ or tumor necrosis factor, detected directly ex vivo. Thus the activation and expansion of MAIT cells coupled with their pro-inflammatory cytokine production occurred in response to Ags derived from microbial riboflavin synthesis and was augmented by co-stimulatory signals.
Formatted abstract
Despite recent breakthroughs in identifying mucosal-associated invariant T (MAIT) cell antigens (Ags), the precise requirements for in vivo MAIT cell responses to infection remain unclear. Using major histocompatibility complex–related protein 1 (MR1) tetramers, the MAIT cell response was investigated in a model of bacterial lung infection employing riboflavin gene-competent and -deficient bacteria. MAIT cells were rapidly enriched in the lungs of C57BL/6 mice infected with Salmonella Typhimurium, comprising up to 50% of αβ-T cells after 1 week. MAIT cell accumulation was MR1-dependent, required Ag derived from the microbial riboflavin synthesis pathway, and did not occur in response to synthetic Ag, unless accompanied by a Toll-like receptor agonist or by co-infection with riboflavin pathway-deficient S. Typhimurium. The MAIT cell response was associated with their long-term accumulation in the lungs, draining lymph nodes and spleen. Lung MAIT cells from infected mice displayed an activated/memory phenotype, and most expressed the transcription factor retinoic acid–related orphan receptor γt. T-bet expression increased following infection. The majority produced interleukin-17 while smaller subsets produced interferon-γ or tumor necrosis factor, detected directly ex vivo. Thus the activation and expansion of MAIT cells coupled with their pro-inflammatory cytokine production occurred in response to Ags derived from microbial riboflavin synthesis and was augmented by co-stimulatory signals.
Keyword Immunology
Immunology
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1016629
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
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Created: Fri, 09 Sep 2016, 21:38:57 EST by Susan Allen on behalf of Institute for Molecular Bioscience