In vitro Control of RNA Virus Infections by M1-Polarized Human Monocyte-Derived Macrophages

Human macrophages are credited with a dual ontogeny: tissue-resident macrophages (TRM) derive from embryonal structures and are endowed with both high resistance to pathogen-induced cell death and homeostatic proliferation in response to self-secreted cytokines. Conversely, circulating monocytes of bone marrow origin can differentiate into macrophages (MDM) upon migration to tissues in response to chemotactic signals triggered by infections or tissue damage. Both TRM and MDM can undergo differential cell activation programs, i.e., "M1/M2 polarization," leading to pro-inflammatory or anti-inflammatory and tissue-remodeling activities, respectively. We here will review the events following in vitro infection of human primary MDM by two unrelated RNA viruses: the human immunodeficiency virus (HIV), a retrovirus causing acquired immunodeficiency syndrome, and Zika virus (ZIKV), a flavivirus associated with microcephaly in newborns. M1 polarization of MDM before infection resulted in a clear-cut containment of the replicative capacity of both HIV-1 and ZIKV, whereas M2-MDM showed a complex modulation of HIV-1 replication and did not affect ZIKV production in human MDM. These findings suggest that M1 polarization of human macrophages contributes to the containment of diverse RNA virus infections, as here exemplified for HIV-1 and ZIKV, and could be harnessed to develop potential host-directed antiviral strategies.