The C andida glabrata adhesin E pa1p causes adhesion, phagocytosis, and cytokine secretion by innate immune cells

While C andida albicans is the most significant fungal pathogen for humans, C andida glabrata accounts for an increasing number of infections. Little is known about how C . glabrata interacts with the innate immune system, the first line of defense against such organisms. The C . glabrata adhesin E pa1p was previously shown to bind mammalian epithelial cells. We hypothesized that E pa1p mediates unique, nonopsonic binding to macrophages, leading to induction of immune responses. We found that E pa1p mediated adhesion by both C . glabrata ( Cg ) and transformed S accharomyces cerevisiae ( Sc EPA1 ) to human macrophage‐like cells, including T hp1 and U 937 lines, and donor PBMC s. Adhesion was distinct from described mechanisms such as D ectin‐1. E pa1p expression was necessary and sufficient for S . cerevisiae binding and phagocytosis, the latter of which was actin‐mediated. Sc EPA1 induced inflammatory cytokine production ( IL ‐8 and TNF ‐α) by human PBMC ‐derived macrophages. Despite expressing E pa1p and binding to macrophages, C g avoided phagocytosis and cytokine induction. In contrast to human results, in murine cell models ( RAW 264.7, J 774A.1, and C 57 BL /6‐derived cells), E pa1p‐mediated binding was only revealed after blocking the D ectin‐1 system. Recognition of E pa1p represents a novel mechanism by which human innate immune cells bind fungi, and for Sc EPA1 results in phagocytosis and subsequent cytokine production.