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.

Potential Role of the Formation of Tunneling Nanotubes in HIV-1 Spread in Macrophages

“…Human peripheral blood monocyte-derived macrophages (MDMs) were prepared as described previously (25,26). Approval for this study was obtained from the Kumamoto University medical ethics committee.…”

“…HIV-1 infection was performed essentially as described previously (26). The MDMs cultured on 24-well tissue culture plates were incubated with 200 ml of the supernatants of 293 cells containing HIV-1 (Gag concentration: 100 ng/ml unless otherwise stated) for 2 h at 37˚C.…”

“…Western blotting was performed as described previously (26). The Abs used were as follows: M-Sec (F-6; Santa Cruz Biotechnology), Gag (#65; BioAcademia, Osaka, Japan), and actin (C-2; Santa Cruz Biotechnology, as a loading control).…”

Colony-Stimulating Factor-1 Receptor in the Polarization of Macrophages: A Target for Turning Bad to Good Ones?

“…These results indicate that, while M1 and M2 activation states can be induced irrespective of a rigid segregation of differentiation signals, it is the balance of these signals (growth factors) which defines the ultimate macrophage activation phenotype [53]. CSF-1R is also able to interfere with IL-32-induced macrophage polarization [54]. IL-32 promotes the differentiation of monocytes into macrophage-like cells and induces the production of various cytokines including TNFα and IL-8, so that it is considered an inducer of M1-like macrophages [55,56].…”

“…These results suggest that IL-32γ induces macrophages with both M1 and M2 phenotypes, and that CSF-1 preferentially accelerates the M2 polarization induced by IL-32γ. Thus, CSF-1 seems to have either additive or inhibitory effects on IL-32γ action as far as the M1 and M2 phenotypes are concerned [54]. [58] where an autocrine mechanism may also be involved [60].…”