Roles of interleukin-17 in an experimental Legionella pneumophila pneumonia model

Yoshifumi Kimizuka, Soichiro Kimura, Tomoo Saga, Makoto Ishii, Naoki Hasegawa, Tomoko Betsuyaku, Yoichiro Iwakura, Kazuhiro Tateda, Keizo Yamaguchi

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Abstract

Interleukin-17 (IL-17) is a key factor in T helper type 17 (Th17) lineage host responses and plays critical roles in immunological control of a variety of infectious diseases. Although Legionella pneumophila, an intracellular bacterium found widely in the environment, often causes a serious and life-threatening pneumonia in humans, the contribution of IL-17 to immune function during Legionella pneumonia is unknown. In the present study, we used an experimental Legionella pneumonia infection to clarify the role of IL-17 in the resulting immune response. We observed robust production of pulmonary IL-17A and IL-17F (IL-17A/ F), peaking on day 1 and declining thereafter. Upregulated production of tumor necrosis factor alpha (TNF-α), IL-6, and IL-1β, but not monocyte chemotactic protein 1 (MCP-1), was observed in Legionella-infected bone marrow-derived macrophages from BALB/c mice that had been stimulated with IL-17A or IL-17F. A significant decrease in the production of proinflammatory cytokines IL-6 and TNF-α was observed in IL-17A/F-deficient mice (BALB/c background) infected with L. pneumophila. Moreover, we found impaired neutrophil migration and lower numbers of chemokines (KC, LIX, and MIP-2) in IL-17A/F-deficient mice. IL-17A/F-deficient mice also eliminated L. pneumophila more slowly and were less likely to survive a lethal challenge. These results demonstrate that IL-17A/F plays a critical role in L. pneumophila pneumonia, probably through induction of proinflammatory cytokines and accumulation of neutrophils at the infection site.

Original languageEnglish
Pages (from-to)1121-1127
Number of pages7
JournalInfection and Immunity
Volume80
Issue number3
DOIs
Publication statusPublished - 2012 Mar 1

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Kimizuka, Y., Kimura, S., Saga, T., Ishii, M., Hasegawa, N., Betsuyaku, T., Iwakura, Y., Tateda, K., & Yamaguchi, K. (2012). Roles of interleukin-17 in an experimental Legionella pneumophila pneumonia model. Infection and Immunity, 80(3), 1121-1127. https://doi.org/10.1128/IAI.05544-11