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

PLoS Pathogens

Katherine Kedzierska¹  Edmond M. Linossi¹  E. Bridie Day¹  Benjamin T. Kile¹  Gabrielle T. Belz²  Donald Metcalf²  Lukasz Kedzierski³  Sandra E. Nicholson³  Nicola L. Bird³  Nicos A. Nicola³  Tatiana B. Kolesnik³ 

[1] Department of Medical Biology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia;Department of Microbiology and Immunology, The University of Melbourne, Parkville, Melbourne, Victoria, Australia;Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria Australia

关键词: T cells;    Cytotoxic T cells;    Cytokines;    Influenza;    Respiratory infections;    Spleen;    Chemokines;    Infectious disease control;   

DOI  :  10.1371/journal.ppat.1004134

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 infection and linked to defects in T cell receptor activation. These results demonstrate that SOCS4 is a critical regulator of anti-viral immunity.

【 授权许可】

CC BY