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

Abstract Candida 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 albicansand C. auris, and explored the inflammation mechanisms of macrophages induced by C. auris. Macrophages showed lower phagocytosis rate, reactive oxygen species production and expression of pro-inflammatory cytokines like IL-6, TNF-α and IL-1β against C. auris when compared with C. 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, TNF-α and IL-1β stimulated by C. auris depended on the activation of TLR2, TLR4, Dectin-1 and downstream signaling pathways. TLR2, TLR4 and Dectin-1 participated in the recognition and phagocytosis of C. auris. We found Dectin-1 was the most important receptor in mediating phagocytosis, while TLR4 was the most critical receptor in influencing inflammatory response. Overall, the study revealed that C. auris induced a lower level of phagocytosis, ROS production and pro-inflammatory factors expression than C. albicans, and TLR2, TLR4 and Dectin-1 played important role in C. auris induced inflammation.