title: Type I IFN suppresses Cxcr2 driven neutrophil recruitment into the sensory ganglia during viral infection.
abstract: Infection induces the expression of inflammatory chemokines that recruit immune cells to the site of inflammation. Whereas tissues such as the intestine and skin express unique chemokines during homeostasis, whether different tissues express distinct chemokine profiles during inflammation remains unclear. With this in mind, we performed a comprehensive screen of the chemokines expressed by two tissues (skin and sensory ganglia) infected with a common viral pathogen (herpes simplex virus type 1). After infection, the skin and ganglia showed marked differences in their expression of the family of Cxcr2 chemokine ligands. Specifically, Cxcl1/2/3, which in turn controlled neutrophil recruitment, was up-regulated in the skin but absent from the ganglia. Within the ganglia, Cxcl2 expression and subsequent neutrophil recruitment was inhibited by type I interferon (IFN). Using a combination of bone marrow chimeras and intracellular chemokine staining, we show that type I IFN acted by directly suppressing Cxcl2 expression by monocytes, abrogating their ability to recruit neutrophils to the ganglia. Overall, our findings describe a novel role for IFN in the direct, and selective, inhibition of Cxcr2 chemokine ligands, which results in the inhibition of neutrophil recruitment to neuronal tissue.
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, the University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Angus T
authors.initials: AT
authors.lastname: Stock
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Smith
authors.forename: Francis R
authors.initials: FR
authors.lastname: Carbone
mesh_terms: D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D017950:Ganglia, Sensory / Q000276:immunology / Q000821:virology; D005786:Gene Expression Regulation / Q000276:immunology*; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007211:Indoles; D007370:Interferon Type I / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D023063:Receptors, Interleukin-8B / Q000378:metabolism*; D012867:Skin / Q000276:immunology / Q000821:virology
chemical_list: D018925:Chemokines; D017931:DNA Primers; D007211:Indoles; D007370:Interferon Type I; D023063:Receptors, Interleukin-8B; C007293:DAPI
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