Macrophage makeover extreme viral edition: mechanisms of immune subversion and therapeutic perspectives

Macrophages are versatile innate immune cells that play a crucial role in immune responses and tissue repair. However, their plasticity and central role in immunity also make them prime targets for viral manipulation. Viruses have evolved sophisticated mechanisms to modulate macrophage functions, disrupting cytokine secretion and phagocytosis to evade immune clearance, establish infection and promote persistence. For instance, some viruses drive excessive cytokine secretion, resulting in hyperinflammation and tissue damage, while other viruses suppress cytokine production and impair phagocytic activity to evade detection. These disruptions often result in systemic immunopathology, chronic inflammation or the establishment of viral reservoirs. Emerging therapeutic strategies aiming to restore macrophage functionality through direct-acting antivirals or macrophage-specific interventions represent a growing interest. These novel approaches offer promising perspectives for combating viral-induced macrophage dysfunction. By summarizing the interplay between viruses and macrophages, this review highlights critical pathways of immune modulation and underscores innovative therapeutic strategies to restore immune balance, offering hope for combating viral infections and their associated pathologies.