C-type Lectin Receptor DCIR Negatively Regulates The Innate Immune Response Induced By Candida Albicans

Innate immunity is the first line of defense in the body's immune response to infection.When pathogens invade the body,pattern recognition receptors(PPRs)expressed on the surface of innate immune cells can recognize different pathogen-associated pattern molecules,such as TLRs,NLRs,RLRs,CLRs,etc.Then they activate downstream signaling pathways to initiate anti-infective immune responses.C-type lectin receptors play multiple roles in the immune system and are central to the identification of fungal carbohydrate fractions and induce innate and adaptive immune responses.When combined with pathogens,CLRs trigger signaling pathways that induce expression of specific cytokines.The classical CLR signaling pathway begins with the activation of Syk,which activates the NF-?B and MAPKs signaling pathways.Once Syk recruits to the CLR complex,intermolecular autophosphorylation occurs,and the activated Syk further promotes activation of downstream signals.The dendritic cell immune receptor DCIR is a type ? CLR expressed on antigen-presenting cells and granulocytes.The intracellular domain contains an immunoreceptor tyrosine-inhibiting motif,which is generally thought to mediate an inhibitory signal.DCIR is expressed in DCs,monocytes,macrophages,B cells,and neutrophils,which has broad specificity for carbohydrates,including mannose and trehalose.This study focuses on the function and role of the C-type lectin receptor DCIR in the process of antifungal activity such as Candida albicans infection.Results showed that DCIR could negatively regulate the inflammatory response during fungal infection,which may be a new mechanism for the body to avoid excessive inflammation during infection.DCIR knockout mice showed higher survival rate,lower tissue damage and fungal load for candida albicans infection.The mechanism may be related to the decrease of Syk recruitment by DCIR by down-regulating the phosphorylation level of SHP2 and the spontaneous phosphorylation of Syk and the activation of downstream signaling pathways,cytokines such as IL-6,IL-12p70,TNF-a and IFN-?.Through in vivo and in vitro experiments,we found that DCIR plays a negative role in regulating inflammation in the innate immune response induced by candida albicans.