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-1 replication by DCs but blocked viral production by M Phis as determined by p24 levels and semiquantitative nested PCR. IL-10 up-regulated CXCR4 mRNA and protein expression on DCs and M Phis, suggesting that IL-10 enhances virus entry in DCs but blocks an entry and/or postentry step in M Phis. The effect of IL-10 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-10 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-10 has opposite effects on the replication of primary X4 HIV-1 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-1-infected patients with disease progression may favor the replication of X4 HIV-1 strains in vivo.
Unité d'Immunopathologie Humaine, Institut National de la Santé et de la Recherche Médicale, Broussais Hospital, Paris, France. ancapetronela@hotmail.com
P
P
Ancuta
Y
Y
Bakri
N
N
Chomont
H
H
Hocini
D
D
Gabuzda
N
N
Haeffner-Cavaillon
D000998:Antiviral Agents / Q000502:physiology; D015704:CD4 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis; D018920:Coculture Techniques; D004279:DNA, Viral / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D015536:Down-Regulation / Q000276:immunology; D018628:Gene Dosage; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D015854:Up-Regulation / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*
D000998:Antiviral Agents; D015704:CD4 Antigens; D018946:Chemokine CCL5; D004279:DNA, Viral; D019718:Receptors, CXCR4; D016753:Interleukin-10