Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0406278 on September 13, 2006

Published online before print September 13, 2006
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(Journal of Leukocyte Biology. 2007;81:642-653.)
© 2007 by Society for Leukocyte Biology

IFN-{gamma}-activated monocytes weakly produce HIV-1 but induce the recruitment of HIV-sensitive T cells and enhance the viral production by these recruited T cells

Héla Saïdi1, Giuliana Magri, Cedric Carbonneil, Nadine Nasreddine, Mary Réquena and Laurent Bélec

Université Paris V, Unité INSERM U743 "Immunologie Humaine," Equipe "Immunité et Biothérapie Muqueuse," Centres de Recherches Biomédicales des Cordeliers, Paris, France

1 Correspondence: Centre de Recherches Biomédicales des Cordeliers, Unité INSERM U743 Equipe "Immunité et Biothérapie Muqueuse," 15 rue de l’Ecole de Médecine, 75270 Paris, Cedex 06, France. E-mail: hela.saidi{at}u430.bhdc.jussieu.fr

ABSTRACT

The ability of macrophages to adapt to changing cytokine environments results in the dominance of a particular functional phenotype of macrophages, which would play a significant role in HIV pathogenesis. In comparison with untreated macrophages (M0), we examined the role of macrophages derived from IFN-{gamma}-activated monocytes (M1) in the HIV spread. We show that M0 and M1 bind with the same efficiency HIV-1 with a predominant role of C-type lectins in the R5-HIV attachment and of the heparan sulfate proteoglycans in the X4-HIV attachment. Despite similar levels of R5- and X4-HIV DNA, M1 replicates and weakly transmits the virus to activated T cells by releasing CXCR4- and CCR5-interacting chemokines. The blockade of dendritic cell-specific ICAM-3-grabbing nonintegrin expressed on M1 by mAb does not interfere with the viral transfer. Uninfected M1 recruits HIV-sensitive T cells efficiently and releases soluble factors, enhancing the viral production by these recruited cells. This study highlights the role of IFN-{gamma} to induce a population of macrophages that archive HIV-1 within a latent stage and cause the persistence of the virus by favoring the recruitment of T cells or enhancing the viral replication in infected CD4+ T cells.

Key Words: adsorption • infection • transfer • cytokines • chemokines







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Copyright © 2007 by the Society for Leukocyte Biology.