Journal Article

Cryptococcus gattii Induces a Cytokine Pattern That Is Distinct from Other Cryptococcal Species

Illnait-Zaragozi, Maria-Teresa, Sprong, Tom, Schoffelen, Teske, Joosten, Leo A. B., Meis, Jacques F., Netea, Mihai G., Boekhout, Teun

2013

Overview

Understanding more about the host's immune response to different Cryptococcus spp. will provide additional insight into the pathogenesis of cryptocococcis. We hypothesized that the ability of C. gattii to cause disease in immunocompetent humans depends on a distinct innate cytokine response of the host to this emerging pathogen. In the current study we assessed the cytokine profile of human peripheral blood mononuclear cells (PBMCs) of healthy individuals, after in vitro stimulation with 40 different well-defined heat-killed isolates of C. gattii, C. neoformans and several hybrid strains. In addition, we investigated the involvement of TLR2, TLR4 and TLR9 in the pro-inflammatory cytokine response to C. gattii. Isolates of C. gattii induced higher concentrations of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6 and the Th17/22 cytokine IL-17 and IL-22 compared to C. neoformans var neoformans and C. neoformans var grubii. In addition, clinical C. gattii isolates induced higher amounts of cytokines than environmental isolates. This difference was not observed in C. neoformans var. grubii isolates. Furthermore, we demonstrated a likely contribution of TLR4 and TLR9, but no role for TLR2, in the host's cytokine response to C. gattii. In conclusion, clinical heat-killed C. gattii isolates induced a more pronounced inflammatory response compared to other Cryptococcus species and non-clinical C. gattii. This is dependent on TLR4 and TLR9 as cellular receptors.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Biology / Candida albicans / Cryptococcus / Cryptococcus - classification / Cryptococcus - immunology / Cryptococcus gattii - immunology / Cryptococcus neoformans / Cytokines / Cytokines - biosynthesis / Cytokines - immunology / Experiments / Fungal infections / Helper cells / Hospitals / Humans / Immune response / Immune system / Infectious diseases / Inflammation / Inflammatory response / Interleukin 17 / Interleukin 22 / Interleukin 6 / Leukocytes (mononuclear) / Leukocytes, Mononuclear - immunology / Leukocytes, Mononuclear - metabolism / Lymphocytes T / Medicine / Microorganisms / Pathogenesis / Pathogens / Pattern recognition / Peripheral blood mononuclear cells / Receptors / Receptors, Pattern Recognition - metabolism / Species Specificity / T cell receptors / TLR2 protein / TLR4 protein / TLR9 protein / Toll-like receptors / Toll-Like Receptors - metabolism / Tumor necrosis factor-TNF / Tumor necrosis factor-α