Journal article

Suppressor of Cytokine Signaling 4 (SOCS4) Protects against Severe Cytokine Storm and Enhances Viral Clearance during Influenza Infection

Lukasz Kedzierski, Edmond M Linossi, Tatiana B Kolesnik, E Bridie Day, Nicola L Bird, Benjamin T Kile, Gabrielle T Belz, Donald Metcalf, Nicos A Nicola, Katherine Kedzierska, Sandra E Nicholson

PLOS PATHOGENS | PUBLIC LIBRARY SCIENCE | Published : 2014

Abstract

Suppressor of cytokine signaling (SOCS) proteins are key regulators of innate and adaptive immunity. There is no described biological role for SOCS4, despite broad expression in the hematopoietic system. We demonstrate that mice lacking functional SOCS4 protein rapidly succumb to infection with a pathogenic H1N1 influenza virus (PR8) and are hypersusceptible to infection with the less virulent H3N2 (X31) strain. In SOCS4-deficient animals, this led to substantially greater weight loss, dysregulated pro-inflammatory cytokine and chemokine production in the lungs and delayed viral clearance. This was associated with impaired trafficking of influenza-specific CD8 T cells to the site of infectio..

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Grants

Awarded by National Health and Medical Research Council (NHMRC), Australia


Awarded by NHMRC IRIISS


Awarded by National Institutes of Health


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

This work was supported in part by the National Health and Medical Research Council (NHMRC), Australia (Program grant #487922, Project grant #1023559), as well as an NHMRC IRIISS grant 361646 and a Victorian State Government Operational Infrastructure Scheme grant. KK is a recipient of an NHMRC CDA2 Fellowship, SEN, BTK and NAN are supported by NHMRC fellowships, GTB is a recipient of an Australian Research Council Fellowship, BTK is supported by a fellowship from the Sylvia and Charles Viertel Foundation, and EML is the recipient of an Australian Postgraduate Award. This work was also supported in part by the National Institutes of Health (RO1 CA22556-26). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.