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.
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.
Saïdi
Héla
H
Université Paris, Unité INSERM U743 Equipe Immunité et Biothérapie Muqueuse, 15 rue de l'Ecole de Médecine, 75270 Paris, Cedex 06, France. hela.saidi@u430.bhdc.jussieu.fr
Magri
Giuliana
G
Carbonneil
Cedric
C
Nasreddine
Nadine
N
Réquena
Mary
M
Bélec
Laurent
L
D002478:Cells, Cultured; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000145:classification / Q000276:immunology / Q000821:virology; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
D007371:Interferon-gamma