Type I IFN signaling constrains IL-17A/F secretion by γδ T cells during bacterial infections

Thomas Henry, Girish S. Kirimanjeswara, Thomas Ruby, Jonathan W. Jones, Kaitian Peng, Magali Perret, Lena Ho, John Demian Sauer, Yoichiro Iwakura, Dennis W. Metzger, Denise M. Monack

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

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+ γδ T cell population, indicating that type I IFNs negatively regulate the number of IL-17A+ γδ 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+ γδ 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.

Original languageEnglish (US)
Pages (from-to)3755-3767
Number of pages13
JournalJournal of Immunology
Volume184
Issue number7
DOIs
StatePublished - Apr 1 2010

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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