IL-23 protection against Plasmodium berghei infection in mice is partially dependent on IL-17 from macrophages

Hidekazu Ishida, Takashi Imai, Kazutomo Suzue, Makoto Hirai, Tomoyo Taniguchi, Akihiko Yoshimura, Yoichiro Iwakura, Hiroko Okada, Tomohisa Suzuki, Chikako Shimokawa, Hajime Hisaeda

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21 Citations (Scopus)

Abstract

Although IL-12 is believed to contribute to protective immune responses, the role played by IL-23 (a member of the IL-12 family) in malaria is elusive. Here, we show that IL-23 is produced during infection with Plasmodium berghei NK65. Mice deficient in IL-23 (p19KO) had higher parasitemia and died earlier than wild-type (WT) controls. Interestingly, p19KO mice had lower numbers of IL-17-producing splenic cells than their WT counterparts. Furthermore, mice deficient in IL-17 (17KO) suffered higher parasitemia than the WT controls, indicating that IL-23-mediated protection is dependent on induction of IL-17 during infection. We found that macrophages were responsible for IL-17 production in response to IL-23. We observed a striking reduction in splenic macrophages in the p19KO and 17KO mice, both of which became highly susceptible to infection. Thus, IL-17 appears to be crucial for maintenance of splenic macrophages. Adoptive transfer of macrophages into macrophage-depleted mice confirmed that macrophage-derived IL-17 is required for macrophage accumulation and parasite eradication in the recipient mice. We also found that IL-17 induces CCL2/7, which recruit macrophages. Our findings reveal a novel protective mechanism whereby IL-23, IL-17, and macrophages reduce the severity of infection with blood-stage malaria parasites.

Original languageEnglish
Pages (from-to)2696-2706
Number of pages11
JournalEuropean Journal of Immunology
Volume43
Issue number10
DOIs
Publication statusPublished - 2013 Oct 1

Keywords

  • IL-17
  • IL-23
  • Macrophage
  • Malaria
  • Plasmodium berghei

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Ishida, H., Imai, T., Suzue, K., Hirai, M., Taniguchi, T., Yoshimura, A., Iwakura, Y., Okada, H., Suzuki, T., Shimokawa, C., & Hisaeda, H. (2013). IL-23 protection against Plasmodium berghei infection in mice is partially dependent on IL-17 from macrophages. European Journal of Immunology, 43(10), 2696-2706. https://doi.org/10.1002/eji.201343493