Macrophage polarization in virus-host interactions

Authors: SANG, YONG-MING - Kansas State University; Miller, Laura; BLECHA, FRANK - Kansas State University

Submitted to: Journal of Clinical & Cellular Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/20/2015
Publication Date: 3/27/2015
Citation: Sang, Y., Miller, L.C., Blecha, F. 2015. Macrophage polarization in virus-host interactions. Journal of Clinical & Cellular Immunology. 6:2.

Interpretive Summary: Infectious diseases cause significant economic loss to U.S. pork producers. Although treating sick animals can help reduce this loss, prevention of disease is the first choice. The best method to prevent transmission of a livestock disease is to induce a protective immune response in susceptible animals through vaccination. For some diseases, current technology is adequate for producing safe and efficacious vaccines. However, for other diseases, vaccines produced from current technology are not adequate. In these cases, understanding the complex nature of the protective immune response may be critical to improving vaccines which requires basic research into how the immune system functions. One important part of the immune response is the activation of different types of cells within the animal's immune system. Macrophages are one of these cell types that are intricately involved in the animal's response to disease. They have a role in the innate responses as well as in development and maintenance of adaptive immunity against invading pathogens. Following infection, the macrophage becomes activated which can occur by direct contact of the macrophage with an infectious agent or indirectly through stimulation of the macrophage by specific proteins produced by other cells in the body. Activated macrophages become polarized meaning the macrophage has developed a certain response against a virus or bacteria. Here, through examination of viral infections targeting macrophages, we elaborate the direct involvement of macrophage polarization during viral infections. Investigating the immunological impact of macrophage polarization may become increasingly important to understanding host-virus interactions of existing and emerging pathogens, with application to the development of novel therapies and vaccine strategies.

Technical 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.