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Opposite Effects of IL-10 on the Ability of Dendritic Cells and Macrophages to Replicate Primary CXCR4-Dependent HIV-1 Strains¹

Petronela Ancuta^2,*, Youssef Bakri^,, Nicolas Chomont^*, Hakim Hocini^*, Dana Gabuzda and Nicole Haeffner-Cavaillon^*

^* Unité d’Immunopathologie Humaine, Institut National de la Santé et de la Recherche Médicale, Broussais Hospital, Paris, France; Institut National de la Santé et de la Recherche Médicale E0013, Faculté de Médicine Saint-Antoine, Paris, France; Laboratoire de Biochimie-Immunologie, JER 3012 associée à l’AUPELF, Faculté de Sciences, Rabat, Morocco; and Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115

We investigated the effect of IL-10 on replication of primary CXCR4-dependent (X4) HIV-1 strains by monocyte-derived dendritic cells (DCs) and macrophages (Ms). Ms efficiently replicated CXCR4-dependent HIV-1 (X4 HIV-1) strains NDK and VN44, whereas low levels of p24 were detected in supernatants of infected DCs. IL-10 significantly increased X4 HIV-1 replication by DCs but blocked viral production by Ms as determined by p24 levels and semiquantitative nested PCR. IL-10 up-regulated CXCR4 mRNA and protein expression on DCs and Ms, suggesting that IL-10 enhances virus entry in DCs but blocks an entry and/or postentry step in Ms. The effect of IL-10 on the ability of DCs and Ms to transmit virus to autologous CD4⁺ T lymphocytes was investigated in coculture experiments. DCs exhibited a greater ability than did Ms to transmit a vigorous infection to CD4⁺ T cells despite their very low replication capacity. IL-10 had no effect on HIV-1 replication in DC:T cell cocultures but markedly decreased viral production in M:T cell cocultures. These results demonstrate that IL-10 has opposite effects on the replication of primary X4 HIV-1 strains by DCs and Ms. IL-10 increases X4-HIV-1 replication in DCs but does not alter their capacity to transmit virus to CD4⁺ T lymphocytes. These findings suggest that increased levels of IL-10 observed in HIV-1-infected patients with disease progression may favor the replication of X4 HIV-1 strains in vivo.

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