Epidemiological studies have consistently shown a linkage between individuals who chronically consume significant amounts of alcohol and hepatitis C viral (HCV) infection. The mechanism by which HCV is able to efficiently evade immune responses is still unknown. It is the purpose of this proposal to study the effects of chronic alcohol consumption on the expression of Toll-like receptors (TLR) and the function of hepatic plasmacytoid (p) dendritic cells (DC). This subset of DC has become of great interest as they are speculated to be primary responders in viral infection, producing large amounts of interferon-alpha upon stimulation. Studies on various TLR have shown that activation through these receptors can modulate the subsequent DC response in a distinct manner and thus influence the activation of T cells. We plan to investigate alterations in the expression and function of these receptors on pDC in established in vitro and in vivo mode s of culture-generated pDC and chronic alcohol consumption. If there are defects in the development of pDC or receptor expression as a result of chronic ethanol intake, it may be possible to promote an appropriate immune response through adoptive transfer of non-ethanol exposed culture-generated pDC. ? ?
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