Opposite effects of IL-10 on the ability of dendritic cells and macrophages to replicate primary CXCR4-dependent HIV-1 strains

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 (M Phis). M Phis 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-I replication by DCs but blocked viral production by M Phis as determined by p24 levels and semiquantitative nested PCR. IL-IO up-regulated CXCR4 mRNA and protein expression on DCs and M Phis, suggesting that IL-IO enhances virus entry in DCs but blocks an entry and/or postentry step in M Phis. The effect of IL-IO on the ability of DCs and M Phis to transmit virus to autologous CD4(+) T lymphocytes was investigated in coculture experiments. DCs exhibited a greater ability than did M Phis to transmit a vigorous infection to CD4(+) T cells despite their very low replication capacity, IL-IO had no effect on HIV-1 replication in DC:T cell cocultures but markedly decreased viral production in M Phi :T cell cocultures. These results demonstrate that IL-IO has opposite effects on the replication of primary X4 HIV-I strains by DCs and M Phis. 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-l-infected patients with disease progression may favor the replication of X4 HIV-1 strains in vivo.