title: Late interleukin-6 escalates T follicular helper cell responses and controls a chronic viral infection.
abstract: Multiple inhibitory molecules create a profoundly immunuosuppressive environment during chronic viral infections in humans and mice. Therefore, eliciting effective immunity in this context represents a challenge. Here, we report that during a murine chronic viral infection, interleukin-6 (IL-6) was produced by irradiation-resistant cells in a biphasic manner, with late IL-6 being absolutely essential for viral control. The underlying mechanism involved IL-6 signaling on virus-specific CD4 T cells that caused up-regulation of the transcription factor Bcl6 and enhanced T follicular helper cell responses at late, but not early, stages of chronic viral infection. This resulted in escalation of germinal center reactions and improved antibody responses. Our results uncover an antiviral strategy that helps to safely resolve a persistent infection in vivo.
authors.affiliation: Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Harker
authors.forename: Gavin M
authors.initials: GM
authors.lastname: Lewis
authors.forename: Lauren
authors.initials: L
authors.lastname: Mack
authors.forename: Elina I
authors.initials: EI
authors.lastname: Zuniga
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000915:Antibody Affinity; D001117:Arenaviridae Infections / Q000276:immunology* / Q000821:virology; D001402:B-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood; D004268:DNA-Binding Proteins / Q000378:metabolism; D018858:Germinal Center / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051560:Proto-Oncogene Proteins c-bcl-6; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; C490010:Bcl6 protein, mouse; D016207:Cytokines; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D051560:Proto-Oncogene Proteins c-bcl-6; D019947:Receptors, Interleukin-6