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

Research output: Contribution to journalArticle

31 Citations (Scopus)

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

Fingerprint

Legionella pneumophila
Interleukin-17
Pneumonia
Legionella
Interleukin-1
Interleukin-6
Neutrophils
Tumor Necrosis Factor-alpha
Cytokines
Chemokine CCL2
Infection
Chemokines
Communicable Diseases
Macrophages
Bacteria

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Roles of interleukin-17 in an experimental Legionella pneumophila pneumonia model. / Kimizuka, Yoshifumi; Kimura, Soichiro; Saga, Tomoo; Ishii, Makoto; Hasegawa, Naoki; Betsuyaku, Tomoko; Iwakura, Yoichiro; Tateda, Kazuhiro; Yamaguchi, Keizo.

In: Infection and Immunity, Vol. 80, No. 3, 03.2012, p. 1121-1127.

Research output: Contribution to journalArticle

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, vol. 80, no. 3, pp. 1121-1127. https://doi.org/10.1128/IAI.05544-11
Kimizuka, Yoshifumi ; Kimura, Soichiro ; Saga, Tomoo ; Ishii, Makoto ; Hasegawa, Naoki ; Betsuyaku, Tomoko ; Iwakura, Yoichiro ; Tateda, Kazuhiro ; Yamaguchi, Keizo. / Roles of interleukin-17 in an experimental Legionella pneumophila pneumonia model. In: Infection and Immunity. 2012 ; Vol. 80, No. 3. pp. 1121-1127.
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