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Interleukin-17 is required for T helper 1 cell immunity and host resistance to the intracellular pathogen Francisella tularensis. 2009
Yinyao Lin, and
Shane Ritchea, and
Alison Logar, and
Samantha Slight, and
Michelle Messmer, and
Javier Rangel-Moreno, and
Lokesh Guglani, and
John F Alcorn, and
Heather Strawbridge, and
Sang Mi Park, and
Reiko Onishi, and
Nikki Nyugen, and
Michael J Walter, and
Derek Pociask, and
Troy D Randall, and
Sarah L Gaffen, and
Yoichiro Iwakura, and
Jay K Kolls, and
Shabaana A Khader
Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.
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-gamma 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.
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