Role of Dectin-2 in the phagocytosis of Cryptococcus neoformans by dendritic cells

Yuki Kitai, Ko Sato, Daiki Tanno, Xiaoliang Yuan, Aya Umeki, Jun Kasamatsu, Emi Kanno, Hiromasa Tanno, Hiromitsu Hara, Sho Yamasaki, Shinobu Saijo, Yoichiro Iwakura, Keiko Ishii, Kazuyoshi Kawakamia

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The cell walls and capsules of Cryptococcus neoformans, a yeast-type fungal pathogen, are rich in polysaccharides. Dectin-2 is a C-type lectin receptor (CLR) that recognizes high-mannose polysaccharides. Previously, we demonstrated that Dectin-2 is involved in cytokine production by bone marrow-derived dendritic cells (BM-DCs) in response to stimulation with C. neoformans. In the present study, we analyzed the role of Dectin-2 in the phagocytosis of C. neoformans by BM-DCs. The engulfment of this fungus by BM-DCs was significantly decreased in mice lacking Dectin-2 (Dectin-2 knockout [Dectin-2KO]) or caspase recruitment domain-containing protein 9 (CARD9KO), a common adapter molecule that delivers signals triggered by CLRs, compared to wild-type (WT) mice. Phagocytosis was likewise inhibited, to a similar degree, by the inhibition of Syk, a signaling molecule involved in CLR-triggered activation. A PI3K inhibitor, in contrast, completely abrogated the phagocytosis of C. neoformans. Actin polymerization, i.e., conformational changes in cytoskeletons detected at sites of contact with C. neoformans, was also decreased in BM-DCs of Dectin-2KO and CARD9KO mice. Finally, the engulfment of C. neoformans by macrophages was significantly decreased in the lungs of Dectin-2KO mice compared to WT mice. These results suggest that Dectin-2 may play an important role in the actin polymerization and phagocytosis of C. neoformans by DCs, possibly through signaling via CARD9 and a signaling pathway mediated by Syk and PI3K.

Original languageEnglish
Article numbere00330-21
JournalInfection and immunity
Volume89
Issue number10
DOIs
Publication statusPublished - 2021 Oct

Keywords

  • Cryptococcus neoformans
  • Immunology
  • Innate immunity
  • Phagocytosis

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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