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

• Published in: Immunity (Cambridge, Mass.) Vol. 39; no. 2; pp. 324 - 334
• Main Authors: Zhu, Le-Le, Zhao, Xue-Qiang, Jiang, Changying, You, Yun, Chen, Xiao-Ping, Jiang, Yuan-Ying, Jia, Xin-Ming, Lin, Xin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.08.2013; Elsevier Limited
• Subjects: Animals; Candida albicans; Candida albicans - immunology; Candidiasis - immunology; Chemokines; Enzyme Activation; Female; Flow cytometry; Humans; Hyphae - immunology; Hyphae - metabolism; Immune system; Infections; Lectins; Lectins, C-Type - deficiency; Lectins, C-Type - genetics; Lectins, C-Type - metabolism; Mannans - metabolism; Membrane Proteins - deficiency; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; NF-kappa B - metabolism; Receptors, Pattern Recognition - immunology; Rodents; Signal Transduction; Studies; Yeast
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2013.05.017

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