MCP-1/CCL2 in Fungal Infections: Balancing Immune Recruitment and Immunopathology

Fungal infections cause substantial morbidity and mortality, particularly in immunocompromised individuals, yet the immune mechanisms that distinguish protective inflammation from tissue-damaging responses remain incompletely understood. Monocyte chemoattractant protein-1, also known as C-C motif chemokine ligand 2 (MCP-1/CCL2), is frequently induced during fungal infection and regulates the recruitment of CCR2-expressing monocytes and other immune-cell populations. This review synthesizes experimental and clinical evidence concerning MCP-1/CCL2 across infections caused by Cryptococcus, Candida, Aspergillus, Pneumocystis, dimorphic fungi, Mucorales, environmental molds, and other fungal species. The available literature shows that MCP-1/CCL2 is neither uniformly protective nor pathogenic. Early and localized production often supports antifungal defense by recruiting functionally competent immune cells, particularly in the lung and at some mucosal surfaces. In contrast, delayed or persistent expression may accompany uncontrolled fungal growth, ineffective chemotaxis, immune reconstitution, and tissue injury, especially in the central nervous system, kidney, cornea, and chronically inflamed airways. Its biological and clinical significance therefore depends on the infected tissue, timing of expression, host immune status, fungal traits, CCR2 function, and the identity and competence of recruited cells. MCP-1/CCL2 is unlikely to serve as a stand-alone biomarker or universal therapeutic target but may be useful in stage-specific therapeutic strategies and biomarker panels.