TY - JOUR
T1 - Impact of chemokine C–C ligand 27, foreskin anatomy and sexually transmitted infections on HIV-1 target cell availability in adolescent South African males
AU - Gray, Clive M.
AU - O’Hagan, Kyle L.
AU - Lorenzo-Redondo, Ramon
AU - Olivier, Abraham J.
AU - Amu, Sylvie
AU - Chigorimbo-Murefu, Nyaradzo
AU - Harryparsad, Rushil
AU - Sebaa, Shorok
AU - Maziya, Lungile
AU - Dietrich, Janan
AU - Otwombe, Kennedy
AU - Martinson, Neil
AU - Ferrian, Selena
AU - Mkhize, Nonhlanhla N.
AU - Lewis, David A.
AU - Lang, Dirk
AU - Carias, Ann M.
AU - Jaspan, Heather B.
AU - Wilson, Douglas P.K.
AU - McGilvray, Marcus
AU - Cianci, Gianguido C.
AU - Anderson, Meegan R.
AU - Dinh, Minh H.
AU - Williamson, Anna Lise
AU - Passmore, Jo Ann S.
AU - Chiodi, Francesca
AU - Hope, Thomas J.
N1 - Funding Information:
This study was supported by grants from the European and Developing Countries Clinical Trials Partnership (EDCTP) Strategic Primer (SP·2011·41304·038), the South African Department of Science and Technology (DST/CON 0260/2012) and the National Institutes of Health (R01 DK108434). K.OH. is supported by the Harry Crossley Foundation and the Claude Leon Foundation. We thank Lynn Morris and Raveshni Durgiah from the National Institute for Communicable Diseases for their help with sample processing. We thank Suzanne Engelbrecht for their invaluable help with confocal and bright-field imaging. Lastly, we thank all participants and staff at Edendale Hospital, Whizzkids United and the Woodstock MMC clinic who were instrumental in recruitment and follow-up of the adolescent boys and young adults in this study and collection of foreskins.
Publisher Copyright:
© 2019, The Author(s).
PY - 2020/1/1
Y1 - 2020/1/1
N2 - We compared outer and inner foreskin tissue from adolescent males undergoing medical male circumcision to better understand signals that increase HIV target cell availability in the foreskin. We measured chemokine gene expression and the impact of sexually transmitted infections (STIs) on the density and location of T and Langerhans cells. Chemokine C–C ligand 27 (CCL27) was expressed 6.94-fold higher in the inner foreskin when compared with the outer foreskin. We show that the density of CD4+CCR5+ cells/mm2 was higher in the epithelium of the inner foreskin, regardless of STI status, in parallel with higher CCL27 gene expression. In the presence of STIs, there were higher numbers of CD4+CCR5+ cells/mm2 cells in the sub-stratum of the outer and inner foreskin with concurrently higher number of CD207+ Langerhans cells (LC) in both tissues, with the latter cells being closer to the keratin surface of the outer FS in the presence of an STI. When we tested the ability of exogenous CCL27 to induce T-cell migration in foreskin tissue, CD4 + T cells were able to relocate to the inner foreskin epithelium in response. We provide novel insight into the impact CCL27 and STIs on immune and HIV-1 target cell changes in the foreskin.
AB - We compared outer and inner foreskin tissue from adolescent males undergoing medical male circumcision to better understand signals that increase HIV target cell availability in the foreskin. We measured chemokine gene expression and the impact of sexually transmitted infections (STIs) on the density and location of T and Langerhans cells. Chemokine C–C ligand 27 (CCL27) was expressed 6.94-fold higher in the inner foreskin when compared with the outer foreskin. We show that the density of CD4+CCR5+ cells/mm2 was higher in the epithelium of the inner foreskin, regardless of STI status, in parallel with higher CCL27 gene expression. In the presence of STIs, there were higher numbers of CD4+CCR5+ cells/mm2 cells in the sub-stratum of the outer and inner foreskin with concurrently higher number of CD207+ Langerhans cells (LC) in both tissues, with the latter cells being closer to the keratin surface of the outer FS in the presence of an STI. When we tested the ability of exogenous CCL27 to induce T-cell migration in foreskin tissue, CD4 + T cells were able to relocate to the inner foreskin epithelium in response. We provide novel insight into the impact CCL27 and STIs on immune and HIV-1 target cell changes in the foreskin.
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U2 - 10.1038/s41385-019-0209-6
DO - 10.1038/s41385-019-0209-6
M3 - Article
C2 - 31619762
AN - SCOPUS:85074572999
VL - 13
SP - 118
EP - 127
JO - Mucosal Immunology
JF - Mucosal Immunology
SN - 1933-0219
IS - 1
ER -
