title: M-CSF inhibits anti-HIV-1 activity of IL-32, but they enhance M2-like phenotypes of macrophages.
abstract: M-CSF promotes the differentiation and survival of macrophages, and preferentially induces anti-inflammatory M2, rather than proinflammatory M1 macrophages. Recently, another cytokine, IL-32, was also shown to promote macrophage differentiation. In this article, we provide the first evidence, to our knowledge, that M-CSF has both additive and inhibitory effects on the macrophage-related activities of IL-32. When added to M-CSF-derived macrophages, M-CSF and IL-32 promoted macrophage survival, which was further enhanced by their combination. However, they had different effects on HIV-1 replication; that is, it was stimulated by M-CSF and inhibited by IL-32. Interestingly, the anti-HIV-1 activity of IL-32 was counteracted by M-CSF. Such inhibitory effect of M-CSF was not observed with IL-32-induced M1-like features including high cytokine/chemokine production and strong expression of the costimulatory molecule CD80. However, IL-32-treated macrophages unexpectedly showed also M2-like features including increased phagocytic activity, and high expression of CD14 and the scavenger receptor CD163, and the expression of CD14 and CD163 was further upregulated by cotreatment with M-CSF. The findings of this study regarding the unique functional interplay between M-CSF and IL-32 increase our understanding of the mechanisms that regulate the survival and M1/M2 ratio of macrophages, as well as HIV-1 replication in macrophages.
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Abu
authors.initials: A
authors.lastname: Osman
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Farzana
authors.initials: F
authors.lastname: Bhuyan
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Hesham
authors.initials: H
authors.lastname: Nasser
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Maekawa
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan ssuzu06@kumamoto-u.ac.jp.
authors.forename: Shinya
authors.initials: S
authors.lastname: Suzu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007378:Interleukins / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C496971:IL32 protein, human; D007378:Interleukins; D016173:Macrophage Colony-Stimulating Factor