Characterization of HIV-1 Infection and Innate Sensing in Different Types of Primary Human Monocyte-Derived Macrophages

• Published in: Mediators of Inflammation Vol. 2013; no. 2013; pp. 1 - 11
• Main Authors: Mogensen, Trine H., Østergaard, Lars, Søby, Stine, Melchjorsen, Jesper, Laursen, Rune R., Berg, Randi K., Diget, Elisabeth A., Zuwala, Kaja
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Limiteds 01.01.2013; Hindawi Puplishing Corporation; Hindawi Publishing Corporation; Hindawi Limited; Wiley
• Subjects: Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Health aspects; HIV infection; HIV Infections - immunology; HIV-1 - immunology; HIV-1 - pathogenicity; Host-parasite relationships; Humans; Immunity, Innate - immunology; Macrophage Colony-Stimulating Factor - metabolism; Macrophages; Macrophages - immunology; Physiological aspects; Virus research
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2013/208412

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.