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Macrophage Immune Responses in Viral Infections: Functional Plasticity and Therapeutic Targeting

Kim J, Lee H, Jang YS

Journal of microbiology and biotechnology, 2026

Abstract

Macrophages play dual roles, contributing to both protection and disease progression during viral infections. As crucial immune cells against pathogens, they activate innate immunity by releasing antiviral agents and inflammatory cytokines. At the same time, they serve as targets for infection and as carriers of viruses, thereby contributing to viral dissemination. This review emphasizes macrophage plasticity and the functional shifts it undergoes during M1/M2 polarization. It also explores mechanisms that maintain persistent viral reservoirs in chronic infections such as SARS-CoV-2 and discusses the impact of macrophage dysregulation on the immune microenvironment. Furthermore, it highlights recent advances in macrophage-targeted therapies, including reprogramming macrophages for homeostasis, eliminating pathogenic macrophages, and boosting antiviral responses.

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