Interleukin-17 Is Required for T Helper 1 Cell Immunity and Host Resistance to the Intracellular Pathogen Francisella tularensis

Yinyao Lin, Shane Ritchea, Alison Logar, Samantha Slight, Michelle Messmer, Javier Rangel-Moreno, Lokesh Guglani, John F. Alcorn, Heather Strawbridge, Sang Mi Park, Reiko Onishi, Nikki Nyugen, Michael J. Walter, Derek Pociask, Troy D. Randall, Sarah L. Gaffen, Yoichiro Iwakura, Jay K. Kolls, Shabaana A. Khader

Research output: Contribution to journalArticlepeer-review

226 Scopus citations

Abstract

The importance of T helper type 1 (Th1) cell immunity in host resistance to the intracellular bacterium Francisella tularensis is well established. However, the relative roles of interleukin (IL)-12-Th1 and IL-23-Th17 cell responses in immunity to F. tularensis have not been studied. The IL-23-Th17 cell pathway is critical for protective immunity against extracellular bacterial infections. In contrast, the IL-23-Th17 cell pathway is dispensable for protection against intracellular pathogens such as Mycobacteria. Here we show that the IL-23-Th17 pathway regulates the IL-12-Th1 cell pathway and was required for protective immunity against F.tularensis live vaccine strain. We show that IL-17A, but not IL-17F or IL-22, induced IL-12 production in dendritic cells and mediated Th1 responses. Furthermore, we show that IL-17A also induced IL-12 and interferon-γ production in macrophages and mediated bacterial killing. Together, these findings illustrate a biological function for IL-17A in regulating IL-12-Th1 cell immunity and host responses to an intracellular pathogen.

Original languageEnglish
Pages (from-to)799-810
Number of pages12
JournalImmunity
Volume31
Issue number5
DOIs
StatePublished - Nov 20 2009

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

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