Abstract
Original language | English |
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Pages (from-to) | 58-68 |
Number of pages | 11 |
Journal | Mucosal Immunology |
Volume | 10 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Jan 2017 |
Cite this
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Mucosal-associated invariant T-cell activation and accumulation after in vivo infection depends on microbial riboflavin synthesis and co-stimulatory signals. / Chen, Z; Wang, H; D'Souza, C; Sun, S; Kostenko, L; Eckle, SBG; Meehan, BS; Jackson, DC; Strugnell, RA; Cao, H; Wang, N; Fairlie, DP; Liu, L; Godfrey, DI; Rossjohn, J; McCluskey, J; Corbett, AJ.
In: Mucosal Immunology, Vol. 10, No. 1, 01.01.2017, p. 58-68.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Mucosal-associated invariant T-cell activation and accumulation after in vivo infection depends on microbial riboflavin synthesis and co-stimulatory signals
AU - Chen, Z
AU - Wang, H
AU - D'Souza, C
AU - Sun, S
AU - Kostenko, L
AU - Eckle, SBG
AU - Meehan, BS
AU - Jackson, DC
AU - Strugnell, RA
AU - Cao, H
AU - Wang, N
AU - Fairlie, DP
AU - Liu, L
AU - Godfrey, DI
AU - Rossjohn, J
AU - McCluskey, J
AU - Corbett, AJ
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85011110731&partnerID=8YFLogxK
U2 - 10.1038/mi.2016.39
DO - 10.1038/mi.2016.39
M3 - Article
VL - 10
SP - 58
EP - 68
JO - Mucosal Immunology
JF - Mucosal Immunology
SN - 1935-3456
IS - 1
ER -