Human hepatitis B virus negatively impacts the protective immune cross‐talk between natural killer and dendritic cells
Claudia De Pasquale
Stefania Campana
Chiara Barberi
Giacomo Sidoti Migliore
Daniela Oliveri
Marika Lanza
Cristina Musolino
Giovanni Raimondo
Soldano Ferrone
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First published: 22 January 2021 https://doi.org/10.1002/hep.31725
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1002/hep.31725
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Abstract
NK cells play a crucial role in the clearance of human viruses but their activity is significantly impaired in chronic hepatitis B infected patients (CHB). Cooperation with dendritic cells (DCs) is pivotal for obtaining optimal NK cell antiviral function, thus we investigated whether HBV might impact the ability of DCs to sustain NK cell functions. Human DCs were poor stimulators of IFN‐γ production by NK cells when exposed to HBV, while maintained capability to trigger NK cell cytotoxicity. HBV prevented DC maturation but did not affect their expression of HLA class I, thus allowing DCs to evade NK cell lysis. Tolerogenic features of DCs exposed to HBV were further supported by their increased expression of IL‐10 and immunosuppressive enzyme indoleamine‐2, 3‐dioxygenase that contributed to the impairment of DC‐mediated NK cell IFN‐γ production and proliferation respectively. HBV could also inhibit the expression of inducible immunoproteasome (iP) subunits on DCs. In fact, NK cells could induce iP subunit expression on DCs but they failed in the presence of HBV. Remarkably, circulating BDCA1+DCs isolated from CHB patients were functionally compromised, hence altering, in turn, NK cell responses. The abnormal NK/DC interplay caused by HBV may significantly impair the efficacy of antiviral immune response in CHB patients. 作者: StephenW 时间: 2021-3-2 17:34