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

Research output: Contribution to journalArticle

17 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

Fingerprint

Interleukin-23
Plasmodium berghei
Interleukin-17
Malaria
Macrophages
Parasitemia
Interleukin-12
Infection
Parasites
Adoptive Transfer
Maintenance

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

IL-23 protection against Plasmodium berghei infection in mice is partially dependent on IL-17 from macrophages. / Ishida, Hidekazu; Imai, Takashi; Suzue, Kazutomo; Hirai, Makoto; Taniguchi, Tomoyo; Yoshimura, Akihiko; Iwakura, Yoichiro; Okada, Hiroko; Suzuki, Tomohisa; Shimokawa, Chikako; Hisaeda, Hajime.

In: European Journal of Immunology, Vol. 43, No. 10, 10.2013, p. 2696-2706.

Research output: Contribution to journalArticle

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, vol. 43, no. 10, pp. 2696-2706. https://doi.org/10.1002/eji.201343493
Ishida, Hidekazu ; Imai, Takashi ; Suzue, Kazutomo ; Hirai, Makoto ; Taniguchi, Tomoyo ; Yoshimura, Akihiko ; Iwakura, Yoichiro ; Okada, Hiroko ; Suzuki, Tomohisa ; Shimokawa, Chikako ; Hisaeda, Hajime. / IL-23 protection against Plasmodium berghei infection in mice is partially dependent on IL-17 from macrophages. In: European Journal of Immunology. 2013 ; Vol. 43, No. 10. pp. 2696-2706.
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