MAIT cells contribute to protection against lethal influenza infection in vivo.
Bonnie van WilgenburgLiyen LohZhenjun ChenTroi J PediongcoHuimeng WangMai ShiZhe ZhaoMarios KoutsakosSimone NüssingSneha SantZhongfang WangCriselle D'SouzaXiaoxiao JiaCatarina F AlmeidaLyudmila KostenkoSidonia Barbara Guiomar EckleBronwyn S MeehanAxel KalliesDale I GodfreyPatrick C ReadingAlexandra J CorbettJames McCluskeyPaul KlenermanKatherine KedzierskaTimothy Stopford Christopher HinksPublished in: Nature communications (2018)
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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- signaling pathway
- cell death
- sars cov
- weight loss
- type diabetes
- coronary artery disease
- bariatric surgery
- skeletal muscle
- pulmonary hypertension
- risk assessment
- metabolic syndrome
- transcription factor
- risk factors
- mesenchymal stem cells
- insulin resistance
- cell proliferation
- long non coding rna
- adipose tissue
- cardiovascular events