Suppressor of cytokine signaling 4 (SOCS4) protects against severe cytokine storm and enhances viral clearance during influenza infection

• Published in: PLoS pathogens Vol. 10; no. 5; p. e1004134
• 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
• Language: English
• Published: United States Public Library of Science 01.05.2014; Public Library of Science (PLoS)
• Subjects: Adaptive Immunity - genetics; Animals; Antiviral agents; B cells; Biology and Life Sciences; Bone marrow; CD8-Positive T-Lymphocytes - immunology; Chemokines; Cytokines; Cytokines - adverse effects; Cytokines - metabolism; Cytoprotection - genetics; Flow cytometry; Health aspects; Immune system; Infections; Inflammation - genetics; Inflammation - metabolism; Inflammation - prevention & control; Inflammation Mediators - adverse effects; Inflammation Mediators - metabolism; Influenza A Virus, H1N1 Subtype - growth & development; Influenza A Virus, H1N1 Subtype - immunology; Kinases; Lungs; Lymphocytes; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Transgenic; Mortality; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - virology; Physiological aspects; Proteins; Scholarships & fellowships; Suppressor of Cytokine Signaling Proteins - physiology; Swine flu; T cell receptors; T cells; Viral infections; Viral Load - genetics; Virulence (Microbiology)
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1004134

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.