ICMI 2015

OR.15 Urethral Macrophages Constitute an Unrecognized Anatomical Reservoir for HIV-1 in the Human Male Genital Tract

Wednesday, July 15, 2015: 11:15 AM
Salon Dublin, Second Floor (Maritim Hotel)
Morgane Bomsel, PhD , Institut Cohin, CNRS, INSERM, Paris, France
Alexis Sennepin, PhD , Institut Cochin, CNRS, INSERM, Paris, France
Charles-Antoine Dutertre, PhD , Institut Cochin, CNRS, INSERM, Singapore, Singapore
Alain Schmitt, Master , Institut Cochin, CNRS, INSERM, Paris, France
Jean-Marc Massé, Ingenieur Assistant , Institut Cochin, CNRS, INSERM, Paris, France
Jean-Pierre Jourdain, Master , Institut Cochin, CNRS, INSERM, Paris, France
Anne Hosmalin, PhD, MD , Institut Cochin, CNRS, INSERM, Paris, France
Yonatan Ganor, PhD , Institut Cochin, CNRS, INSERM, Paris, France
SourceURL:file:///AAAAA%20/%20%20%20%20%20Textes/%20%20%20%20%20Abstracts/2015,%20Urethral%20Reser%23EEF498.doc

HIV-1 eradication, or at least functional cure, requires the elimination/reduction of the HIV-1 reservoir pool. Residual viremia in HIV-1-infected-HAART-treated patients originates not only from memory CD4+ T-cells, the best-studied cellular HIV-1-reservoirs, but also from other cell types, especially tissues-resident macrophages. We recently identified male urethral macrophages as a novel and highly efficient entry site for HIV-1. We now evaluated whether the urethra serves as a yet unrecognized anatomical reservoir for HIV-1 in direct link with the initial HIV-1 infection of urethral macrophages.

Accordingly, HIV-1 was detected by ISH in CD68+macrophages but not in T-cells in urethral tissues from HIV-1+ patients under effective anti-viral therapy. In these tissues, macrophages contained the HIV-1 capsid protein p24 (by IF); formed conjugates with CD3+T-cells (by IHC); and harbored virions in virus-containing-compartment(VCC)-like structures (ultrastructurally by EM). Hence, despite HARRT, HIV-1 persists in urethral macrophages. Importantly, HIV-1 could be amplified from single-cell suspensions prepared from urethral tissues, following LPS treatment and subsequent contact with activated CD4+T cells. Macrophages polarization in tissues plays a crucial role in orientating the local immune response towards pro- or anti-inflammatory activities. Cell surface characterization of macrophage subsets in normal urethra  by flow cytometry showed that M1 outnumber M2-macrophages, and revealed the presence of an new M1/M2 ‘intermediate’ subset. In infected urethral tissues from HAART treated patients, the CD163+M2 population disappeared whereas the proportion of the mixed M1/M2 intermediate subset increased. Altogether, these results suggest an active role for resident urethral macrophages inHIV-1 infection, which also serve as novel HIV-1 reservoirs