title: Type I IFN signaling constrains IL-17A/F secretion by gammadelta T cells during bacterial infections.
abstract: Recognition of intracellular bacteria by macrophages leads to secretion of type I IFNs. However, the role of type I IFN during bacterial infection is still poorly understood. Francisella tularensis, the causative agent of tularemia, is a pathogenic bacterium that replicates in the cytosol of macrophages leading to secretion of type I IFN. In this study, we investigated the role of type I IFNs in a mouse model of tularemia. Mice deficient for type I IFN receptor (IFNAR1(-/-)) are more resistant to intradermal infection with F. tularensis subspecies novicida (F. novicida). Increased resistance to infection was associated with a specific increase in IL-17A/F and a corresponding expansion of an IL-17A(+) gammadelta T cell population, indicating that type I IFNs negatively regulate the number of IL-17A(+) gammadelta T cells during infection. Furthermore, IL-17A-deficient mice contained fewer neutrophils compared with wild-type mice during infection, indicating that IL-17A contributes to neutrophil expansion during F. novicida infection. Accordingly, an increase in IL-17A in IFNAR1(-/-) mice correlated with an increase in splenic neutrophil numbers. Similar results were obtained in a mouse model of pneumonic tularemia using the highly virulent F. tularensis subspecies tularensis SchuS4 strain and in a mouse model of systemic Listeria monocytogenes infection. Our results indicate that the type I IFN-mediated negative regulation of IL-17A(+) gammadelta T cell expansion is conserved during bacterial infections. We propose that this newly described activity of type I IFN signaling might participate in the resistance of the IFNAR1(-/-) mice to infection with F. novicida and other intracellular bacteria.
authors.affiliation: Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Henry
authors.forename: Girish S
authors.initials: GS
authors.lastname: Kirimanjeswara
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruby
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Jones
authors.forename: Kaitian
authors.initials: K
authors.lastname: Peng
authors.forename: Magali
authors.initials: M
authors.lastname: Perret
authors.forename: Lena
authors.initials: L
authors.lastname: Ho
authors.forename: John-Demian
authors.initials: JD
authors.lastname: Sauer
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Metzger
authors.forename: Denise M
authors.initials: DM
authors.lastname: Monack
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D005434:Flow Cytometry; D007370:Interferon Type I / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014406:Tularemia / Q000276:immunology / Q000378:metabolism
chemical_list: D007370:Interferon Type I; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta