Impact of chemokine C–C ligand 27, foreskin anatomy and sexually transmitted infections on HIV-1 target cell availability in adolescent South African males

Clive M. Gray*, Kyle L. O’Hagan, Ramon Lorenzo-Redondo, Abraham J. Olivier, Sylvie Amu, Nyaradzo Chigorimbo-Murefu, Rushil Harryparsad, Shorok Sebaa, Lungile Maziya, Janan Dietrich, Kennedy Otwombe, Neil Martinson, Selena Ferrian, Nonhlanhla N. Mkhize, David A. Lewis, Dirk Lang, Ann M. Carias, Heather B. Jaspan, Douglas P.K. Wilson, Marcus McGilvrayGianguido C. Cianci, Meegan R. Anderson, Minh H. Dinh, Anna Lise Williamson, Jo Ann S. Passmore, Francesca Chiodi, Thomas J. Hope

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)118-127
Number of pages10
JournalMucosal Immunology
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Gray, C. M., O’Hagan, K. L., Lorenzo-Redondo, R., Olivier, A. J., Amu, S., Chigorimbo-Murefu, N., Harryparsad, R., Sebaa, S., Maziya, L., Dietrich, J., Otwombe, K., Martinson, N., Ferrian, S., Mkhize, N. N., Lewis, D. A., Lang, D., Carias, A. M., Jaspan, H. B., Wilson, D. P. K., ... Hope, T. J. (2020). Impact of chemokine C–C ligand 27, foreskin anatomy and sexually transmitted infections on HIV-1 target cell availability in adolescent South African males. Mucosal Immunology, 13(1), 118-127. https://doi.org/10.1038/s41385-019-0209-6