Cryptococcus gattii evades CD11b-mediated fungal recognition by coating itself with capsular polysaccharides

Eur J Immunol. 2021 Sep;51(9):2281-2295. doi: 10.1002/eji.202049042. Epub 2021 Mar 30.

Abstract

Cryptococcus gattii is a capsular pathogenic fungus causing life-threatening cryptococcosis. Although the capsular polysaccharides (CPs) of C. gattii are considered as virulence factors, the physiological significance of CP biosynthesis and of CPs themselves is not fully understood, with many conflicting data reported. First, we demonstrated that CAP gene deletant of C. gattii completely lacked capsule layer and its virulence, and that the strain was susceptible to host-related factors including oxidizing, hypoxic, and hypotrophic conditions in vitro. Extracellular CPs recovered from culture supernatant bound specifically to C. gattii acapsular strains, not to other fungi and immune cells, and rendered them the immune escape effects. In fact, dendritic cells (DCs) did not efficiently uptake the CP-treated acapsular strains, which possessed no visible capsule layer, and a decreased amount of phosphorylated proteins and cytokine levels after the stimulation. DCs recognized C. gattii acapuslar cells via an immune receptor CD11b- and Syk-related pathway; however, CD11b did not bind to CP-treated acapsular cells. These results suggested that CPs support immune evasion by coating antigens on C. gattii and blocking the interaction between CD11b and C. gattii cells. Here, we describe the importance of CPs in pathogenicity and immune evasion mechanisms of C. gattii.

Keywords: Cryptococcus gattii; capsular polysaccharides; dendritic cells; fungal recognition; integrins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11b Antigen / immunology*
  • Cryptococcosis / immunology
  • Cryptococcus gattii / genetics
  • Cryptococcus gattii / immunology*
  • Cryptococcus gattii / pathogenicity
  • Cytokines / biosynthesis
  • Dendritic Cells / immunology
  • Female
  • Fungal Capsules / genetics
  • Fungal Capsules / immunology*
  • Fungal Polysaccharides / genetics
  • Fungal Polysaccharides / immunology*
  • Gene Deletion
  • Humans
  • Immune Evasion / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Polysaccharides / genetics
  • Polysaccharides / immunology
  • Syk Kinase / metabolism*
  • Virulence Factors / immunology

Substances

  • CD11b Antigen
  • Cytokines
  • Fungal Polysaccharides
  • Itgam protein, mouse
  • Polysaccharides
  • Virulence Factors
  • galactoxylomannan
  • glucuronoxylomannan
  • Syk Kinase
  • Syk protein, mouse