Candida auris induces phagocytosis, reactive oxygen species production and inflammation through TLR2, TLR4 and Dectin-1 dependent signaling in macrophages

Abstract

Candida auris (C. auris) is an important fungal pathogen with high rates of transmissibility, mortality, and drug resistance. However, studies on its pathogenicity, host-pathogen interactions, and macrophage immune responses against C. auris are still limited. This study compared the immune response induced by Candida albicans and C. auris, and explored the inflammation mechanisms of macrophages induced by C. auris. Macrophages showed a lower phagocytosis rate, reactive oxygen species production, and expression of pro-inflammatory cytokines like interleukin (IL)-6, tumor necrosis factor-α and IL-1β against C. auris when compared with Candida albicans. To further study the mechanism of inflammatory response induced by C. auris, macrophages were stimulated with C. auris for different concentration and duration. The expression and secretion of IL-6, tumor necrosis factor-α and IL-1β stimulated by C. auris depended on the activation of Toll-like receptor 2 (TLR2), TLR4, Dectin-1, and downstream signaling pathways. TLR2, TLR4, and Dectin-1 participated in the recognition and phagocytosis of C. auris. Dectin-1 was the most important receptor in mediating immune response, while TLR4 was the most critical receptor in influencing the inflammatory response. Overall, the study revealed that C. auris induced a lower level of phagocytosis, production of reactive oxygen species, and expression of inflammatory factors than Candida albicans, and that TLR2, TLR4, and Dectin-1 played important roles in the induction of inflammation.