title: SOCS4 is dispensable for an efficient recall response to influenza despite being required for primary immunity.
abstract: Suppressor of cytokine signaling (SOCS) proteins are key regulators of innate and adaptive immunity. Mice lacking functional SOCS4 are hypersusceptible to primary infection with influenza A virus (IAV), displaying dysregulated pro-inflammatory cytokine and chemokine production in the lungs, delayed viral clearance and impaired trafficking of influenza-specific CD8(+) T cells to the site of infection. Therefore, we postulated that SOCS4 is a critical regulator of anti-viral immunity. Unexpectedly, SOCS4 was not required for CD8(+) T-cell memory generation, nor was it required to efficiently recall those cells in response to secondary IAV infection. Wild-type or SOCS4-deficient mice primed and re-challenged with serologically different influenza strains, did not show differences in susceptibility to IAV and cleared the virus from the lungs at the same rate. We have not observed differences in trafficking or numbers of IAV-specific cells, numbers of resident memory T cells or in cytokine profiles in lungs of infected animals. Our data show that despite an impaired primary immune response in Socs4(R108X/R108X) mice, SOCS4 is dispensable for an efficient recall response to influenza virus infection.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kedzierski
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
authors.forename: E Bridie
authors.initials: EB
authors.lastname: Clemens
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Bird
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Benjamin T
authors.identifier: http://orcid.org/0000-0002-8836-8947
authors.initials: BT
authors.lastname: Kile
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Nicos A
authors.initials: NA
authors.lastname: Nicola
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kedzierska
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Nicholson
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002465:Cell Movement / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D007109:Immunity / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D016130:Immunophenotyping; D008168:Lung / Q000502:physiology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; C473084:SOCS4 protein, human; D050826:Suppressor of Cytokine Signaling Proteins