C-Type Lectin Receptors Dectin-3 and Dectin-2 Form a Heterodimeric Pattern-Recognition Receptor for Host Defense against Fungal Infection

C-type lectin receptors (CLRs) play critical roles as pattern-recognition receptors (PRRs) for sensing Candida albicans infection, which can be life-threatening for immunocompromised individuals. Here we have shown that Dectin-3 (also called CLECSF8, MCL, or Clec4d), a previously uncharacterized CLR, recognized α-mannans on the surfaces of C. albicans hyphae and induced NF-κB activation. Mice with either blockade or genetically deleted Dectin-3 were highly susceptible to C. albicans infection. Dectin-3 constantly formed heterodimers with Dectin-2, a well-characterized CLR, for recognizing C. albicans hyphae. Compared to their respective homodimers, Dectin-3 and Dectin-2 heterodimers bound α-mannans more effectively, leading to potent inflammatory responses against fungal infections. Together, our study demonstrates that Dectin-3 forms a heterodimeric PRR with Dectin-2 for sensing fungal infection and suggests that different CLRs may form different hetero- and homodimers, which provide different sensitivity and diversity for host cells to detect various microbial infections. [Display omitted] •Dectin-3 is a subunit of a functional PRR that senses Candida albicans infection•Dectin-3-deficient mice are highly susceptible to fungal infection•Dectin-2 and Dectin-3 form a heterodimeric pattern-recognition receptor•Dectin-2 and Dectin-3 heterodimers have a high affinity for PAMP