Suppressor of Cytokine Signaling 4 (SOCS4) Protects against Severe Cytokine Storm and Enhances Viral Clearance during Influenza Infection e1004134

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 pa...

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Bibliographic Details
Published inPLoS pathogens Vol. 10; no. 5
Main Authors Kedzierski, Lukasz, Linossi, Edmond M, Kolesnik, Tatiana B, Day, E Bridie, Bird, Nicola L, Kile, Benjamin T, Belz, Gabrielle T, Metcalf, Donald, Nicola, Nicos A, Kedzierska, Katherine, Nicholson, Sandra E
Format Journal Article
LanguageEnglish
Published San Francisco Public Library of Science 01.05.2014
Subjects
Bone marrow
Chemokines
Cytokines
Flow cytometry
Immune system
Infections
Kinases
Lungs
Lymphocytes
Mortality
Proteins
Scholarships & fellowships
Swine flu
T cell receptors
Viral infections
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Summary: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.
ISSN:1553-7366
1553-7374
DOI:10.1371/journal.ppat.1004134