title: C-C chemokines released by lipopolysaccharide (LPS)-stimulated human macrophages suppress HIV-1 infection in both macrophages and T cells.
abstract: Human immunodeficiency virus-1 (HIV-1) expression in monocyte-derived macrophages (MDM) infected in vitro is known to be inhibited by lipopolysaccharide (LPS). However, the mechanisms are incompletely understood. We show here that HIV-1 suppression is mediated by soluble factors released by MDM stimulated with physiologically significant concentrations of LPS. LPS-conditioned supernatants from MDM inhibited HIV-1 replication in both MDM and T cells. Depletion of C-C chemokines (RANTES, MIP-1 alpha, and MIP-1 beta) neutralized the ability of LPS-conditioned supernatants to inhibit HIV-1 replication in MDM. A combination of recombinant C-C chemokines blocked HIV-1 infection as effectively as LPS. Here, we report an inhibitory effect of C-C chemokines on HIV replication in primary macrophages. Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.
authors.affiliation: Department of Biological and Technological Research, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Verani
authors.forename: G
authors.initials: G
authors.lastname: Scarlatti
authors.forename: M
authors.initials: M
authors.lastname: Comar
authors.forename: E
authors.initials: E
authors.lastname: Tresoldi
authors.forename: S
authors.initials: S
authors.lastname: Polo
authors.forename: M
authors.initials: M
authors.lastname: Giacca
authors.forename: P
authors.initials: P
authors.lastname: Lusso
authors.forename: A G
authors.initials: AG
authors.lastname: Siccardi
authors.forename: D
authors.initials: D
authors.lastname: Vercelli
mesh_terms: D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism / Q000494:pharmacology; D018925:Chemokines / Q000378:metabolism / Q000494:pharmacology*; D004279:DNA, Viral / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000821:virology*; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5; D018121:Receptors, Cytokine / Q000096:biosynthesis; D015728:Receptors, HIV / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D014779:Virus Replication / Q000187:drug effects
chemical_list: D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D004279:DNA, Viral; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D014409:Tumor Necrosis Factor-alpha