title: C-type lectin receptors Dectin-3 and Dectin-2 form a heterodimeric pattern-recognition receptor for host defense against fungal infection.
abstract: 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.
authors.affiliation: Department of Immunology, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Le-Le
authors.initials: LL
authors.lastname: Zhu
authors.forename: Xue-Qiang
authors.initials: XQ
authors.lastname: Zhao
authors.forename: Changying
authors.initials: C
authors.lastname: Jiang
authors.forename: Yun
authors.initials: Y
authors.lastname: You
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
authors.forename: Yuan-Ying
authors.initials: YY
authors.lastname: Jiang
authors.forename: Xin-Ming
authors.initials: XM
authors.lastname: Jia
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D025301:Hyphae / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008351:Mannans / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000276:immunology; D015398:Signal Transduction
chemical_list: C113583:Clecsf8 protein, mouse; D037181:Lectins, C-Type; D008351:Mannans; D008565:Membrane Proteins; D016328:NF-kappa B; D051192:Receptors, Pattern Recognition; C445340:dectin-2, mouse