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Comparable mRNA expression of inflammatory markers but lower claudin-1 mRNA levels in foreskin tissue of HSV-2 seropositive versus seronegative asymptomatic Kenyan young men.

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posted on 12.05.2016, 00:00 by M Röhl, A Tjernlund, SD Mehta, V Pettersson, RC Bailey, K Broliden
OBJECTIVES: Skin biopsies from local sites of herpes simplex virus 2 (HSV-2)-induced ulcers can show infiltrates of inflammatory cells several months after macroscopic healing. We hypothesise that foreskin tissue samples of asymptomatic HSV-2 seropositive men had remaining signs of inflammation at the molecular level. Even in the absence of clinical lesions, genital inflammation may contribute to increased HIV susceptibility on sexual exposure to the virus. SETTING: Foreskin tissue samples were collected from men undergoing elective circumcision in Kisumu, Kenya. PARTICIPANTS: The foreskin tissue samples (n=86) were stratified into study groups based on HSV-2 serology and assessed for mRNA expression of inflammatory markers. Markers of interest were further assessed by immunohistochemical staining within the tissue samples. RESULTS: The two study groups had comparable levels of all molecular markers (CD3, CD4, CD8, CD69, CCR5, HLA-DR, Langerin, DC-SIGN, Mannose Receptor 1, IL-1, IL-6, TNF-α, β7, IgA, IFN-α, CCL5, E-cadherin, ZO-1 and occludin), except for lower mRNA levels of the epithelial junction protein claudin-1 in the HSV-2 seropositive group (p=0.008). Although mRNA levels of claudin-1 were lower in HSV-2 seropositive individuals, the corresponding protein could be visualised in the foreskin epithelium of all samples tested. CONCLUSIONS: Whereas no general inflammation was demonstrated in the foreskin of asymptomatic HSV-2 seropositive individuals, a decreased expression of claudin-1 indicates a less robust genital epithelial barrier. An intact epithelial barrier is essential for blocking mucosal entry of genital infections, including HIV.

Funding

g This work was supported by the Swedish Research Council [to KB], the Swedish International Development Cooperation Agency, SIDA/SAREC (to KB), and from the National Institute of Allergy and Infectious Diseases (NIAID), Division of AIDS, National Institute of Health (NIH) (to RCB, AI50440). RCB was partially supported by the Chicago Developmental Centre for AIDS Research (D-CFAR), an NIH funded programme (P30 AI 082151).

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Publisher Statement

This is a copy of an article published in the BMJ Open © 2015 BMJ Publishing Group.

Publisher

BMJ Publishing Group

issn

2044-6055

Issue date

18/02/2015

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