title: Abundant expression of HIV target cells and C-type lectin receptors in the foreskin tissue of young Kenyan men.
abstract: A biological explanation for the reduction in HIV-1 (HIV) acquisition after male circumcision may be that removal of the foreskin reduces the number of target cells for HIV. The expression of potential HIV target cells and C-type lectin receptors in foreskin tissue of men at risk of HIV infection were thus analyzed. Thirty-three foreskin tissue samples, stratified by Herpes simplex virus type 2 status, were obtained from a randomized, controlled trial conducted in Kenya. The samples were analyzed by confocal in situ imaging microscopy and mRNA quantification by quantitative RT-qPCR. The presence and location of T cells (CD3(+)CD4(+)), Langerhans cells (CD1a(+)Langerin/CD207(+)), macrophages (CD68(+) or CD14(+)), and submucosal dendritic cells (CD123(+)BDCA-2(+) or CD11c(+)DC-SIGN(+)) were defined. C-type lectin receptor expressing cells were detected in both the epithelium and submucosa, and distinct lymphoid aggregates densely populated with CD3(+)CD4(+) T cells were identified in the submucosa. Although the presence of lymphoid aggregates and mRNA expression of selected markers varied between study subjects, Herpes simplex virus type 2 serostatus was not the major determinant for the detected differences. The detection of abundant and superficially present potential HIV target cells and submucosal lymphoid aggregates in foreskin mucosa from a highly relevant HIV risk group demonstrate a possible anatomical explanation that may contribute to the protective effect of male circumcision on HIV transmission.
authors.affiliation: Center for Molecular Medicine, Infectious Disease Unit, Department of Medicine, Solna, Karolinska Institutet, 171 76 Stockholm, Sweden. taha.hirbod@ki.se
authors.forename: Taha
authors.initials: T
authors.lastname: Hirbod
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bailey
authors.forename: Kawango
authors.initials: K
authors.lastname: Agot
authors.forename: Stephen
authors.initials: S
authors.lastname: Moses
authors.forename: Jeckoniah
authors.initials: J
authors.lastname: Ndinya-Achola
authors.forename: Ruth
authors.initials: R
authors.lastname: Murugu
authors.forename: Jan
authors.initials: J
authors.lastname: Andersson
authors.forename: Jakob
authors.initials: J
authors.lastname: Nilsson
authors.forename: Kristina
authors.initials: K
authors.lastname: Broliden
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D002986:Clinical Trials as Topic; D052816:Foreskin / Q000166:cytology / Q000378:metabolism / Q000821:virology; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D018258:Herpesvirus 2, Human / Q000378:metabolism; D006801:Humans; D007630:Kenya; D037181:Lectins, C-Type / Q000378:metabolism*; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D037181:Lectins, C-Type
references.citation: J Clin Pathol. 2004 Jan;57(1):77-8
references.pmid: 14693841
references.citation: AIDS. 2006 Jul 13;20(11):1491-5
references.pmid: 16847403
references.citation: J Virol. 2007 Jul;81(13):6858-68
references.pmid: 17442711
references.citation: AIDS. 2009 Jan 28;23(3):319-28
references.pmid: 19114867
references.citation: Lancet. 2007 Feb 24;369(9562):657-66
references.pmid: 17321311
references.citation: Am J Pathol. 2002 Sep;161(3):867-73
references.pmid: 12213715
references.citation: Nat Immunol. 2002 Oct;3(10):975-83
references.pmid: 12352970
references.citation: Nat Med. 2007 Mar;13(3):367-71
references.pmid: 17334373
references.citation: Nat Rev Immunol. 2005 Dec;5(12):953-64
references.pmid: 16322748
references.citation: Curr Infect Dis Rep. 2008 May;10(2):121-7
references.pmid: 18462586
references.citation: Immunology. 1995 Jul;85(3):475-84
references.pmid: 7558138
references.citation: Immunity. 2007 Feb;26(2):257-70
references.pmid: 17306567
references.citation: Biol Reprod. 2005 Dec;73(6):1253-63
references.pmid: 16093359
references.citation: J Biol Chem. 1990 Jul 25;265(21):12156-62
references.pmid: 2373685
references.citation: J Virol. 2002 Oct;76(19):9868-76
references.pmid: 12208964
references.citation: Am J Clin Pathol. 2006 Mar;125(3):386-91
references.pmid: 16613341
references.citation: Int Urol Nephrol. 2009 Dec;41(4):747-53
references.pmid: 19184514
references.citation: AIDS. 2009 Sep 10;23(14):1807-15
references.pmid: 19584700
references.citation: PLoS Med. 2005 Nov;2(11):e298
references.pmid: 16231970
references.citation: J Acquir Immune Defic Syndr. 2006 Sep;43(1):69-77
references.pmid: 16878046
references.citation: J Clin Invest. 2004 Mar;113(5):701-8
references.pmid: 14991068
references.citation: Cell. 2000 Mar 3;100(5):587-97
references.pmid: 10721995
references.citation: J Exp Med. 2004 Apr 19;199(8):1065-75
references.pmid: 15078900
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Science. 2009 Mar 27;323(5922):1726-9
references.pmid: 19325114
references.citation: Lancet. 2007 Feb 24;369(9562):643-56
references.pmid: 17321310
references.citation: Nat Med. 2009 Aug;15(8):886-92
references.pmid: 19648930
references.citation: J Acquir Immune Defic Syndr. 2009 Jul 1;51(3):239-47
references.pmid: 19363450
references.citation: J Virol. 2005 Mar;79(5):3117-26
references.pmid: 15709031
references.citation: Lab Invest. 1992 Nov;67(5):628-34
references.pmid: 1434540
references.citation: AIDS. 2008 Aug 20;22(13):1667-71
references.pmid: 18670228
references.citation: J Immunol. 2008 Nov 1;181(9):5829-35
references.pmid: 18941170