Macrophage states and polarization during Mycobacterium tuberculosis infection: mechanisms, granuloma adaptation, and host-directed therapeutic opportunities
TL;DR
The molecular mechanisms underlying macrophage polarization during Mtb infection are synthesized, the bidirectional regulatory networks between pathogen-derived and host-derived factors are integrated, and their roles in immune evasion, granuloma biology, and emerging therapeutic strategies in tuberculosis are highlighted.
Abstract
Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb). As primary host cells targeted by Mtb, macrophages play central roles in both innate and adaptive immunity. Accumulating evidence indicates that macrophage polarization is a key determinant of tuberculosis pathogenesis. In response to diverse microenvironmental cues, macrophages adopt functionally distinct polarization states, ranging from pro-inflammatory, microbicidal programs (M1-like) to anti-inflammatory, tissue-reparative programs (M2-like). These states differentially shape tuberculosis progression. Defining the remodeling of these context-dependent macrophage states is therefore critical for understanding Mtb infection, granuloma formation, and disease outcomes, as well as for guiding the development of next-generation vaccines, immunotherapies, and host-directed interventions. This Review synthesizes the molecular mechanisms underlying macrophage polarization during Mtb infection, integrates the bidirectional regulatory networks between pathogen-derived and host-derived factors, and highlights their roles in immune evasion, granuloma biology, and emerging therapeutic strategies in tuberculosis.