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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30AA015235-02
Application #
6952671
Study Section
Special Emphasis Panel (ZAA1-EE (10))
Program Officer
Gentry, Thomas
Project Start
2004-09-13
Project End
2008-09-12
Budget Start
2005-09-13
Budget End
2006-09-12
Support Year
2
Fiscal Year
2005
Total Cost
$54,113
Indirect Cost
Name
University of Pittsburgh
Department
Surgery
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Winger, Beth Apsel; Foy, Eileen; Sud, Sohil R et al. (2016) Mycobacterium bovis Enterocolitis in an Immunocompromised Host. J Pediatr Gastroenterol Nutr 63:e17-9
Lau, Audrey H; Szabo, Gyongyi; Thomson, Angus W (2009) Antigen-presenting cells under the influence of alcohol. Trends Immunol 30:13-22
Lau, Audrey H; Thomson, Angus W; Colvin, Bridget L (2007) Chronic ethanol exposure affects in vivo migration of hepatic dendritic cells to secondary lymphoid tissue. Hum Immunol 68:577-85
Lau, Audrey H; Abe, Masanori; Thomson, Angus W (2006) Ethanol affects the generation, cosignaling molecule expression, and function of plasmacytoid and myeloid dendritic cell subsets in vitro and in vivo. J Leukoc Biol 79:941-53