Intestinal lymphocyte subsets and turnover are affected by chronic alcohol consumption: implications for SIV/HIV infection.
We recently demonstrated that simian immunodeficiency virus (SIV) viral loads were significantly higher in the plasma of rhesus macaques consuming alcohol compared with controls following intrarectal SIV infection. To understand the possible reasons behind increased viral replication, here we assessed the effects of chronic alcohol consumption on distribution and cycling of various lymphocyte subsets in the intestine. Macaques were administered alcohol (n = 11) or sucrose (n = 12), and percentages of memory and naive and activated lymphocyte subsets were compared in the blood, lymph nodes, and intestines. Although minimal differences were detected in blood or lymph nodes, there were significantly higher percentages of central memory (CD95+CD28+) CD4+ lymphocytes in the intestines from alcohol-receiving animals before infection compared with controls. In addition, higher percentages of naive (CD45RA+CD95-) as well as CXCR4+CD4 cells were detected in intestines of alcohol-treated macaques. Moreover, alcohol consumption resulted in significantly lower percentages of effector memory (CD95+CD28-) CD8 lymphocytes as well as activated Ki67+CD8 cells in the intestines. A subset (7 receiving alcohol and 8 receiving sucrose) were then intrarectally inoculated with SIV(mac251). Viral RNA was compared in different tissues using real-time PCR and in situ hybridization. Higher levels of SIV replication were observed in tissues from alcohol-consuming macaques compared with controls. Central memory CD4 lymphocytes were significantly depleted in intestines and mesenteric lymph nodes from all alcohol animals at 8 weeks postinfection. Thus, changes in the mucosal immune compartment (intestines) in response to alcohol are likely the major reasons behind higher replication of SIV observed in these animals.
Poonia
Bhawna
B
Division of Comparative Pathology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA.
Nelson
Steve
S
Bagby
Greg J
GJ
Veazey
Ronald S
RS
D000428:Alcohol Drinking / Q000276:immunology*; D000818:Animals; D018791:CD4 Lymphocyte Count; D003106:Colon / Q000276:immunology; D004195:Disease Models, Animal; D006678:HIV / Q000235:genetics / Q000302:isolation & purification; D015658:HIV Infections / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D008253:Macaca mulatta; D008297:Male; D012367:RNA, Viral / Q000097:blood / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000302:isolation & purification; D013154:Spleen / Q000276:immunology; D019562:Viral Load
D012367:RNA, Viral