Immune activation in HIV/HCV-infected patients is associated with low-level expression of liver expressed antimicrobial peptide-2 (LEAP-2).
BACKGROUND
Immune activation is one of the main features of HIV/Hepatitis C virus (HCV) infections and has been linked to the disturbance of the gut-associated lymphoid tissue (GALT). In chronic HIV infection, loss of GALT integrity results in translocation of microbial products and chronic immune activation. We explored the relationship between bacterial translocation and specific colonic proteins, including liver expressed antimicrobial peptide (LEAP 2) which may play a role in modulating the bacterial translocation process.


METHODS
A total of 40 subjects (10 HIV/HCV, 10 HIV, 10 HCV-infected patients and 10 controls) were enrolled and underwent serum and colonic tissue sampling. The levels of immune activation were evaluated by measuring plasma sCD27, and the levels of selected proinflammatory, Th2 and regulatory cytokines in both the plasma and supernatant of CD3-stimulated intraepithelial lymphocytes. We also evaluated LEAP-2 expression in the colon biopsies using Affymetrix Human Gene 1.0 ST (HuGene) and fluorescent immunohistochemistry.


RESULTS
Increased levels of sCD27 were observed in HIV/HCV coinfected (p=0.03) and HIV monoinfected (p=0.04) patients compared with controls consistent with the presence of immune activation. The chip array identified LEAP-2 expression as a key marker associated with immune activation. LEAP-2 expression in HIV, HCV and HIV/HCV-infected patients was significantly lower compared with controls, and was significantly negatively correlated (p=0.03, r=-0.44) with sCD27.


CONCLUSIONS
Our data suggests that HCV and HIV infections are associated with decreased expression of LEAP-2 in colonic tissue. This may represent a key mechanism for enhanced microbial translocation and immune activation in HIV/HCV-infected patients.
Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati, , Cincinnati, Ohio, USA.
Mohamed Tarek M
MT
Shata
Enass A
EA
Abdel-Hameed
Helal F
HF
Hetta
Kenneth E
KE
Sherman
D000328:Adult; D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D018988:Bacterial Translocation; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D060085:Coinfection; D003106:Colon / Q000276:immunology / Q000473:pathology / Q000821:virology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D006801:Humans; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood; D055815:Young Adult
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D016207:Cytokines; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C475606:liver-expressed antimicrobial peptide 2, human
HIV; Hepatitis; Immunopathology; Liver; Microbial Pathogenic