MAIT cells contribute to protection against lethal influenza infection in vivo

Bonnie van Wilgenburg, Liyen Loh, Zhenjun Chen, Troi J Pediongco, Huimeng Wang, Mai Shi, Zhe Zhao, Marios Koutsakos, Simone Nüssing, Sneha Sant, Zhongfang Wang, Criselle D’Souza, Catarina F Almeida, Lyudmila Kostenko, Sidonia BG Eckle, Bronwyn S Meehan, Dale I Godfrey, Patrick C Reading, Alexandra J Corbett, James McCluskey, Paul Klenerman, Katherine Kedzierska and Timothy SC Hinks

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May 07, 2018
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Received: 9th April 18

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 accumulated and were activated early in infection, with upregulation of CD25, CD69 and Granzyme B, peaking at 5 days post infection. Activation was modulated via cytokines independently of MR1. MAIT cell-deficient MR1-/- mice showed enhanced weight loss and mortality to severe (H1N1) influenza. This was ameliorated by prior adoptive transfer of pulmonary MAIT cells in both immunocompetent and immunodeficient RAG2-/-, gC-/- mice. Thus, MAIT cells contribute to protection during respiratory viral infections, and constitute a potential target for therapeutic manipulation.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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