Dectin-2-mediated signaling triggered by the cell wall polysaccharides of Cryptococcus neoformans

Daiki Tanno, Rin Yokoyama, Kotone Kawamura, Yuki Kitai, Xiaoliang Yuan, Keiko Ishii, Magdia De Jesus, Hideki Yamamoto, Ko Sato, Tomomitsu Miyasaka, Hiroki Shimura, Nobuyuki Shibata, Yoshiyuki Adachi, Naohito Ohno, Sho Yamasaki, Kazuyoshi Kawakami

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Cryptococcus neoformans is rich in polysaccharides of the cell wall and capsule. Dectin-2 recognizes high-mannose polysaccharides and plays a central role in the immune response to fungal pathogens. Previously, we demonstrated Dectin-2 was involved in the activation of dendritic cells upon stimulation with C. neoformans, suggesting the existence of a ligand recognized by Dectin-2. In the present study, we examined the cell wall structures of C. neoformans contributing to the Dectin-2-mediated activation of immune cells. In a NFAT-GFP reporter assay of the reported cells expressing Dectin-2, the lysates, but not the whole yeast cells, of an acapsular strain of C. neoformans (Cap67) delivered Dectin-2-mediated signaling. This activity was detected in the supernatant of β-glucanase-treated Cap67 and more strongly in the semi-purified polysaccharides of this supernatant using ConA-affinity chromatography (ConA-bound fraction), in which a large amount of saccharides, but not protein, were detected. Treatment of this supernatant with periodic acid and the addition of excessive mannose, but not glucose or galactose, strongly inhibited this activity. The ConA-bound fraction of the β-glucanase-treated Cap67 supernatant was bound to Dectin-2-Fc fusion protein in a dose-dependent manner and strongly induced the production of interleukin-12p40 and tumour necrosis factor-α by dendritic cells; this was abrogated under the Dectin-2-deficient condition. Finally, 98 kDa mannoprotein (MP98) derived from C. neoformans showed activation of the reporter cells expressing Dectin-2. These results suggested that a ligand with mannose moieties may exist in the cell walls and play a critical role in the activation of dendritic cells during infection with C. neoformans.

Original languageEnglish
Pages (from-to)500-512
Number of pages13
JournalMICROBIOLOGY and IMMUNOLOGY
Volume63
Issue number12
DOIs
Publication statusPublished - 2019 Dec 1
Externally publishedYes

Keywords

  • C-type lectin receptors
  • Cryptococcus neoformans
  • Dectin-2 ligands
  • anti-fungal immunity
  • mannoproteins

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

Fingerprint Dive into the research topics of 'Dectin-2-mediated signaling triggered by the cell wall polysaccharides of Cryptococcus neoformans'. Together they form a unique fingerprint.

Cite this