Conclusion
HBV may exploit CLR pathways to hijack DC subsets and escape from immune control. Such advances bring insights into the mechanisms by which HBV subverts immunity and pave the way for developing innovative therapeutic strategies to restore an efficient immune control of the infection by manipulating the viral glycan-lectin axis.
Methods
We investigated here the pattern of CLR expression on BDCA1+ cDC2s, BDCA2+ pDCs and BDCA3+ cDC1s from both blood and liver of HBV-infected patients and explored the ability of HBsAg to bind DC subsets through specific CLRs.
Results
We highlighted for the first time that the CLR repertoire of circulating and intrahepatic cDC2s, cDC1s and pDCs was perturbed in patients with chronic HBV infection and that some CLR expression levels correlated with plasma HBsAg and HBV DNA levels. We also identified candidate CLR responsible for HBsAg binding to cDCs (CD367/DCIR/CLEC4A, CD32/FcɣRIIA) and pDCs (CD369/DECTIN1/CLEC7A, CD336/NKp44) and demonstrated that HBsAg inhibited DC functions in a CLR- and glycosylation-dependent manner.