title: Characterization of HIV-1 infection and innate sensing in different types of primary human monocyte-derived macrophages.
abstract: Macrophages play an important role in human immunodeficiency virus (HIV) pathogenesis and contribute to establishment of a viral reservoir responsible for continuous virus production and virus transmission to T cells. In this study, we investigated the differences between various monocyte-derived macrophages (MDMs) generated through different differentiation protocols and evaluated different cellular, immunological, and virological properties. We found that elevated and persistent HIV-1 pWT/BaL replication could be obtained only in MDMs grown in RPMI containing macrophage colony-stimulating factor (M-CSF). Interestingly, this MDM type was also most responsive to toll-like receptor stimulation. By contrast, all MDM types were activated to a comparable extent by intracellular DNA, and the macrophage serum-free medium-(Mac-SFM-)differentiated MDMs responded strongly to membrane fusion through expression of CXCL10. Finally, we found that HIV infection of RPMI/M-CSF-differentiated MDMs induced low-grade expression of two interferon-stimulated genes in some donors. In conclusion, our study demonstrates that the differentiation protocol used greatly influences the ability of MDMs to activate innate immune reactions and support HIV-1 replication. Paradoxically, the data show that the MDMs with the strongest innate immune response were also the most permissive for HIV-1 replication.
authors: Department of Infectious Diseases, Aarhus University Hospital, Skejby, 8200 Aarhus, Denmark.
authors: Elisabeth A
authors: EA
authors: Diget
authors: Kaja
authors: K
authors: Zuwala
authors: Randi K
authors: RK
authors: Berg
authors: Rune R
authors: RR
authors: Laursen
authors: Stine
authors: S
authors: Søby
authors: Lars
authors: L
authors: Østergaard
authors: Jesper
authors: J
authors: Melchjorsen
authors: Trine H
authors: TH
authors: Mogensen
mesh_terms: D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*
chemical_list: D016173:Macrophage Colony-Stimulating Factor