The interplay between Natural killer (NK) cells and Dendritic cells (DCs) represents a first line of defence against viral infections. NK/DC interaction results in reciprocal cell activation and production of Interferon-γ (IFN-γ), a major antiviral cytokine. Chronic Hepatitis B (CHB) virus infection is characterized by a marked immune dysfunction that involves also NK cells, since IFN-γ production by NK cells is significantly reduced in both peripheral blood and liver of CHB infected patients. Considering the crucial role of DCs in stimulating NK cell response, we sought to determine whether DCs could be responsible for NK cell impairment, as a consequence of HBV infection. To this purpose, DCs were cultured in the presence of highly viremic sera from CHB patients and their phenotype and functions analysed. In the presence of HBV serum, a drastic inhibition of DC maturation occurred, as demonstrated by the low expression of maturation markers, co-stimulatory molecules and IL-12, the latter representing a key cytokine for IFN-γ production by NK cells. Accordingly, DCs conditioned by the serum were significantly impaired in inducing both IFN-γ and TNF-α production by NK cells as well as in inducing NK cell proliferation. Similar data were obtained by adding HBV particles to DC cultures, suggesting that HBV has a direct role in the functional impairment of DCs. In addition, the inhibitory role of HBV on DCs was apparently also exerted by a significant up-regulation of the tolerogenic enzyme Indoleamine 2 3-dioxygenase (IDO), which played a major role in the inhibition of NK cell proliferation induced by DCs. Altogether, our data revealed that serum from chronic HBV patients significantly impairs DC functions and, in turn, both proliferation and IFN-γ production by NK cells upon DC/NK interactions. HBV is directly responsible for the phenotypic and functional alterations observed in DCs, suggesting that, during HBV chronic infection, abnormalities in the interactions between DCs and NK cells might occur, thus resulting in a reduced antiviral response.
|Titolo:||Hepatitis B Virus affects Dendritic cell activation and their cross-talk with Natural Killer cells|
|Data di pubblicazione:||30-nov-2017|
|Appare nelle tipologie:||Tesi di dottorato|