Open AccessCryptococcus gattii alters immunostimulatory potential in response to the environment
Author(s) -
Keigo Ueno,
Yoshiko Otani,
Nao Yanagihara,
Takumi Nakamura,
Kiminori Shimizu,
Satoshi Yamagoe,
Yoshitsugu Miyazaki
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0220989
Subject(s) - cryptococcus gattii , cryptococcus neoformans , cryptococcosis , microbiology and biotechnology , biology , cryptococcus , candida albicans , yeast , innate immune system , pathogen , agar , immune system , immunology , bacteria , biochemistry , genetics
Cryptococcus gattii is a capsular fungal pathogen, which causes life-threatening cryptococcosis in immunocompetent individuals. This emerging pathogen is less likely to be recognized by innate immunity compared to traditional Cryptococcus neoformans strains. Previous studies indicate that C-type lectin receptors (CLRs), including dectin-1 and dectin-2, play a role in recognizing cryptococcal cells; however, it remains to be elucidated whether the receptors physically associate with C . gattii yeast cell surfaces. Based on the previous findings, we hypothesized that culture conditions influence the expression or exposure of CLR ligands on C . gattii . Therefore, in the present study, we first investigated the culture conditions that induce exposure of CLR ligands on C . gattii yeast cells via the binding assay using recombinant fusion proteins of mouse CLR and IgG Fc, Fc dectin-1 and Fc dectin-2. Common fungal culture media, such as yeast extract–peptone–dextrose (YPD) broth, Sabouraud broth, and potato dextrose agar, did not induce the exposure of dectin-1 ligands, including β-1,3-glucan, on both capsular and acapsular C . gattii strains, in contrast to Fc dectin-1 and Fc dectin-2 bound to C . gattii cells growing in the conventional synthetic dextrose (SD) medium [may also be referred to as a yeast nitrogen base with glucose medium]. The medium also induced the exposure of dectin-1 ligands on C . neoformans , whereas all tested media induced dectin-1 and dectin-2 ligands in a control fungus Candida albicans . Notably, C . gattii did not expose dectin-1 ligands in SD medium supplemented with yeast extract or neutral buffer. In addition, compared to YPD medium-induced C . gattii , SD medium-induced C . gattii more efficiently induced the phosphorylation of Syk, Akt, and Erk1/2 in murine dendritic cells (DCs). Afterwards, the cells were considerably engulfed by DCs and remarkably induced DCs to secrete the inflammatory cytokines. Overall, the findings suggest that C . gattii alters its immunostimulatory potential in response to the environment.