Limited role of mincle in the host defense against infection with cryptococcus deneoformans

Yuki Sato, Ko Sato, Hideki Yamamoto, Jun Kasamatsu, Tomomitsu Miyasaka, Daiki Tanno, Anna Miyahara, Takafumi Kagesawa, Akiho Oniyama, Kotone Kawamura, Rin Yokoyama, Yuki Kitai, Aya Umeki, Shigenari Ishizuka, Kazuki Takano, Ryuhei Shiroma, Nana Nakahata, Kaori Kawakami, Emi Kanno, Hiromasa TannoSho Yamasaki, Hiromitsu Hara, Keiko Ishii, Kazuyoshi Kawakamia

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Cryptococcus deneoformans is an opportunistic fungal pathogen that frequently causes fatal meningoencephalitis in patients with impaired cell-mediated immune responses such as AIDS. Caspase-associated recruitment domain 9 (CARD9) plays a critical role in the host defense against cryptococcal infection, suggesting the involvement of one or more C-type lectin receptors (CLRs). In the present study, we analyzed the role of macrophage-inducible C-type lectin (Mincle), one of the CLRs, in the host defense against C. deneoformans infection. Mincle expression in the lungs of wild-type (WT) mice was increased in the early stage of cryptococcal infection in a CARD9-dependent manner. In Mincle gene-disrupted (Mincle KO) mice, the clearance of this fungus, pathological findings, Th1/Th2 response, and antimicrobial peptide production in the infected lungs were nearly comparable to those in WT mice. However, the production of interleukin-22 (IL-22), tumor necrosis factor alpha (TNF-α), and IL-6 and the expression of AhR were significantly decreased in the lungs of Mincle KO mice compared to those of WT mice. In in vitro experiments, TNF-α production by bone marrow-derived dendritic cells was significantly decreased in Mincle KO mice. In addition, the disrupted lysates of C. deneoformans, but not those of whole yeast cells, activated Mincle-triggered signaling in an assay with a nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) reporter cells expressing this receptor. These results suggest that Mincle may be involved in the production of Th22-related cytokines at the early stage of cryptococcal infection, although its role may be limited in the host defense against infection with C. deneoformans.

Original languageEnglish
Article numbere00400
JournalInfection and immunity
Volume88
Issue number11
DOIs
Publication statusPublished - 2020 Nov

Keywords

  • Cryptococcus deneoformans
  • Host defense
  • Mincle
  • Th22

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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