Fungal pattern-recognition receptors and tetraspanins: partners on antigen-presenting cells

Fungal pattern-recognition receptors (F-PRRs), including C-type lectins, Toll-like receptors, scavenger receptors and Fc/complement receptors, are crucial for inducing anti-fungal immune responses by antigen-presenting cells. The recent identification of specific F-PRR interactions with tetraspanins has shed new light on the functioning of F-PRRs in the cell membrane and subsequent downstream signaling. Tetraspanins are small four-transmembrane proteins that can assemble immune receptors and signaling molecules into functional membrane microdomains. Here, we discuss the implications of this novel type of interaction between F-PRRs and tetraspanins in different subsets of antigen-presenting cells. We postulate that upon fungal binding tetraspanins modulate the function of F-PRRs by their recruitment into tetraspanin microdomains, leading to immune activation or tolerance.