title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Foreskin tissue samples were collected from men undergoing elective circumcision in Kisumu, Kenya.
  
  
  METHODS
  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.
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna, Karolinska University Hospital, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Röhl
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna, Karolinska University Hospital, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Annelie
authors.initials: A
authors.lastname: Tjernlund
authors.affiliation: Division of Epidemiology, School of Public Health, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Supriya D
authors.initials: SD
authors.lastname: Mehta
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna, Karolinska University Hospital, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Pettersson
authors.affiliation: Division of Epidemiology, School of Public Health, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bailey
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna, Karolinska University Hospital, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Broliden
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D062445:Claudin-1 / Q000378:metabolism*; D052816:Foreskin / Q000378:metabolism*; D015658:HIV Infections / Q000209:etiology*; D006558:Herpes Genitalis / Q000150:complications / Q000378:metabolism* / Q000821:virology; D018258:Herpesvirus 2, Human; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D007630:Kenya; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D062445:Claudin-1; D018836:Inflammation Mediators; D012333:RNA, Messenger
keywords: IMMUNOLOGY; VIROLOGY