Mx1 Reveals Innate Pathways to Antiviral Resistance and Lethal Influenza Disease

Overview

Journal Science

Specialty Science

Date 2016 Apr 23

PMID 27102485

Citations 147

Authors

Padmini S Pillai

Ryan D Molony

Kimberly Martinod

Huiping Dong

Iris K Pang

Michal C Tal

Angel G Solis

Piotr Bielecki

Subhasis Mohanty

Mark Trentalange

Robert J Homer

Richard A Flavell

Denisa D Wagner

Ruth R Montgomery

Albert C Shaw

Peter Staeheli

Akiko Iwasaki

Affiliations

Soon will be listed here.

Abstract

Influenza A virus (IAV) causes up to half a million deaths worldwide annually, 90% of which occur in older adults. We show that IAV-infected monocytes from older humans have impaired antiviral interferon production but retain intact inflammasome responses. To understand the in vivo consequence, we used mice expressing a functional Mx gene encoding a major interferon-induced effector against IAV in humans. In Mx1-intact mice with weakened resistance due to deficiencies in Mavs and Tlr7, we found an elevated respiratory bacterial burden. Notably, mortality in the absence of Mavs and Tlr7 was independent of viral load or MyD88-dependent signaling but dependent on bacterial burden, caspase-1/11, and neutrophil-dependent tissue damage. Therefore, in the context of weakened antiviral resistance, vulnerability to IAV disease is a function of caspase-dependent pathology.

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