Abstract
ObjectivesC‐type lectin receptors (CLRs) are key receptors used by DCs to orchestrate responses to pathogens. During infections, the glycan–lectin interactions shape the virus–host interplay and viruses can subvert the function of CLRs to escape antiviral immunity. Recognition of virus/viral components and uptake by CLRs together with subsequent signalling cascades are crucial in initiating and shaping antiviral immunity, and decisive in the outcome of infection. Yet, the interaction of hepatitis B virus (HBV) with CLRs remains largely unknown. As HBV hijacks DC subsets and viral antigens harbour glycan motifs, we hypothesised that HBV may subvert DCs through CLR binding.MethodsWe 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.ResultsWe 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.ConclusionHBV 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.
Highlights
Dendritic cells (DCs) are professional antigenpresenting cells (APCs) specialised in the orchestration of antiviral immune responses.[1,2] DCs own a unique ability to detect invading pathogens, capture and cross-present viral antigens to effector cells and provide additional signals that trigger innate and adaptive immune responses against viral infections
Three major DC subsets exist in human blood and are found in liver[5,6,7]: myeloid or conventional CD11c+ DCs subdivided into two subsets based on the differential expression of CD1c/BDCA1 and CD141/BDCA3 molecules,[4] and plasmacytoid DCs which are CD11c– BDCA2+ BDCA4+8
As DCs are crucial in binding carbohydrate moieties of pathogens to mediate immune responses, we investigated the basal expression of specific C-type lectin receptors (CLRs) molecules among peripheral and intrahepatic CD11c+ DCs (cDCs) and plasmacytoid DCs (pDCs)
Summary
Dendritic cells (DCs) are professional antigenpresenting cells (APCs) specialised in the orchestration of antiviral immune responses.[1,2] DCs own a unique ability to detect invading pathogens, capture and cross-present viral antigens to effector cells and provide additional signals that trigger innate and adaptive immune responses against viral infections. There are specialised DC subsets that differ in ontology, localisation, surface marker expression, molecular phenotype, cytokine production, and antigen-processing and presentation capacity.[4] Three major DC subsets exist in human blood and are found in liver[5,6,7]: myeloid or conventional CD11c+ DCs (cDCs) subdivided into two subsets based on the differential expression of CD1c/BDCA1 (cDC2s) and CD141/BDCA3 (cDC1s) molecules,[4] and plasmacytoid DCs (pDCs) which are CD11c– BDCA2+ BDCA4+8. Each DC subset displays its own repertoire of TLRs and a specific pattern of CLRs that endowed them with a functional specialisation and tightly regulate their response.[9,10]
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