Present in all tissues, they constitute the first line of defense of the innate immune system. Their ability to recognize pathogens, produce cytokines, and phagocytose targets enables them to coordinate immune responses and maintain tissue homeostasis. This functional plasticity, essential for adaptation to local environments, nevertheless represents a vulnerability exploited by many viruses.

This review synthesizes the mechanisms by which different viruses modulate macrophage functions to promote their replication, dissemination, or persistence. Some viruses trigger excessive activation of inflammatory pathways, notably through transcription factors such as NF-κB or via inflammasome activation. This hyperactivation leads to massive production of pro-inflammatory cytokines, contributing to immunopathological phenomena such as cytokine storm syndromes observed in certain severe viral infections. Conversely, other viruses inhibit antiviral responses by blocking type I interferon production or interfering with pathogen recognition pathways, thereby weakening the ability of macrophages to control infection.

Viruses can also impair phagocytosis, a key process for eliminating infectious agents and infected cells. By disrupting cytoskeletal organization, phagosome maturation, or the expression of receptors involved in particle uptake, they reduce the efficiency of this essential function. These alterations not only promote viral persistence but also increase susceptibility to secondary infections, particularly bacterial ones.

A central point addressed in this review is the diversity of virus-macrophage interactions depending on the context. In some cases, macrophages are directly infected and contribute to viral production or to the amplification of the inflammatory response. In other situations, they act as sentinel cells, responding to signals emitted by infected cells without themselves being productive targets. This distinction strongly influences the immunological and pathological consequences of viral infections.

Finally, the authors discuss the therapeutic perspectives arising from these observations. In addition to antivirals that directly target viruses, innovative approaches aim to modulate macrophage functions in order to restore an effective immune response without inducing harmful inflammation. These so-called “host-directed” strategies could offer new options for the treatment of acute or chronic infections associated with dysregulation of innate immunity.