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Nat Commun. 2018 Nov 9;9(1):4706. doi: 10.1038/s41467-018-07207-9.
MAIT cells contribute to protection against lethal influenza infection in vivo.
Wilgenburg BV1,2, Loh L1, Chen Z1, Pediongco TJ1, Wang H1, Shi M1, Zhao Z1, Koutsakos M1, N?ssing S1, Sant S1, Wang Z1, D'Souza C1, Jia X1, Almeida CF1,3, Kostenko L1, Eckle SBG1, Meehan BS1, Kallies A1, Godfrey DI1,3, Reading PC1, Corbett AJ1, McCluskey J1, Klenerman P4, Kedzierska K1, Hinks TSC1,5.
Author information
Abstract
Mucosal associated invariant T (MAIT) cells are evolutionarily-conserved, innate-like lymphocytes which are abundant in human lungs and can contribute to protection against pulmonary bacterial infection. MAIT cells are also activated during human viral infections, yet it remains unknown whether MAIT cells play a significant protective or even detrimental role during viral infections in vivo. Using murine experimental challenge with two strains of influenza A virus, we show that MAIT cells accumulate and are activated early in infection, with upregulation of CD25, CD69 and Granzyme B, peaking at 5 days post-infection. Activation is modulated via cytokines independently of MR1. MAIT cell-deficient MR1-/- mice show enhanced weight loss and mortality to severe (H1N1) influenza. This is ameliorated by prior adoptive transfer of pulmonary MAIT cells in both immunocompetent and immunodeficient RAG2-/-γC-/- mice. Thus, MAIT cells contribute to protection during respiratory viral infections, and constitute a potential target for therapeutic manipulation.
PMID: 30413689 DOI: 10.1038/s41467-018-07207-9
MAIT cells contribute to protection against lethal influenza infection in vivo.
Wilgenburg BV1,2, Loh L1, Chen Z1, Pediongco TJ1, Wang H1, Shi M1, Zhao Z1, Koutsakos M1, N?ssing S1, Sant S1, Wang Z1, D'Souza C1, Jia X1, Almeida CF1,3, Kostenko L1, Eckle SBG1, Meehan BS1, Kallies A1, Godfrey DI1,3, Reading PC1, Corbett AJ1, McCluskey J1, Klenerman P4, Kedzierska K1, Hinks TSC1,5.
Author information
Abstract
Mucosal associated invariant T (MAIT) cells are evolutionarily-conserved, innate-like lymphocytes which are abundant in human lungs and can contribute to protection against pulmonary bacterial infection. MAIT cells are also activated during human viral infections, yet it remains unknown whether MAIT cells play a significant protective or even detrimental role during viral infections in vivo. Using murine experimental challenge with two strains of influenza A virus, we show that MAIT cells accumulate and are activated early in infection, with upregulation of CD25, CD69 and Granzyme B, peaking at 5 days post-infection. Activation is modulated via cytokines independently of MR1. MAIT cell-deficient MR1-/- mice show enhanced weight loss and mortality to severe (H1N1) influenza. This is ameliorated by prior adoptive transfer of pulmonary MAIT cells in both immunocompetent and immunodeficient RAG2-/-γC-/- mice. Thus, MAIT cells contribute to protection during respiratory viral infections, and constitute a potential target for therapeutic manipulation.
PMID: 30413689 DOI: 10.1038/s41467-018-07207-9