Macrophage Polarization in Virus-Host Interactions

Abstract

Macrophage involvement in viral infections and antiviral states is common. However, this involvement has not been well-studied in the paradigm of macrophage polarization, which typically has been categorized by the dichotomy of classical (M1) and alternative (M2) statuses. Recent studies have revealed the complexity of macrophage polarization in response to various cellular mediators and exogenous stimuli by adopting a multipolar view to revisit the differential process of macrophages, especially those re-polarized during viral infections. Here, through examination of viral infections targeting macrophages/monocytic cells, we focus on the direct involvement of macrophage polarization during viral infections. Type I and type III interferons (IFNs) are critical in regulation of viral pathogenesis and host antiviral infection; thus, we propose to incorporate IFN-mediated antiviral states into the framework of macrophage polarization. This view is supported by the multifunctional properties of type I IFNs, which potentially elicit and regulate both M1- and M2-polarization in addition to inducing the antiviral state, and by the discoveries of viral mechanisms to adapt and modulate macrophage polarization. Indeed, several recent studies have demonstrated effective prevention of viral diseases through manipulation of macrophage immune statuses.

Porcine alveolar macrophage polarization is involved in inhibition of porcine reproductive and respiratory syndrome virus (PRRSV) replication

“…However, when M1-type cells were infected 48 hr after polarization in the present study, no inhibitory effects on PRRSV replication were observed. To some extent, the phenotype of polarized M1-M2 macrophages can be reversed in vitro and in vivo [ 12 , 28 ]. Indeed, our unpublished data demonstrated that M0-/M1-type PAMs were re-polarized to the M2 type as a result of HP-PRRSV infection.…”

Evolutionary Aspects of Macrophages Polarization

“…Although macrophage adaptability provides a selective advantage in host resistance to pathogen, this same plasticity can sometimes be exploited and subverted by pathogens to invade the host. Indeed, in mammals, it is not infrequent in an infectious disease setting to find pathology associated with dynamic changes in macrophage activation, where M1 macrophages are associated with initiating and sustaining inflammation and M2 macrophages are associated with either resolution or chronic infection (Cassetta et al 2011; Herbein and Varin 2010; Labonte et al 2014; Sang et al 2015; Shaked et al 2014). Interestingly, in mouse models, the polarized M1/M2 phenotypes can, to some extent, be experimentally reversed in vitro and in vivo, which makes macrophages interesting targets for immune-modulation and therapeutic applications (Guiducci et al 2005; Saccani et al 2006).…”

RNA editing enzyme APOBEC3A promotes pro-inflammatory (M1) macrophage polarization

“…Viral infections can drive M1 polarization that in turn enhances antiviral immunity. IFN-1 plays a role in M1 polarization of macrophages exposed to virus infection (Sang et al, 2015). Accordingly, IFN-1 concentration was detectable in the media of macrophages infected by the Maraba virus (Figure 2B).…”