Regulatory cells, including regulatory T cells (Tregs), regulatory B cells (Bregs), and myeloid-derived suppressor cells (MDSCs), play a critical role in maintaining immune tolerance and controlling immune responses during infections. However, pathogens have evolved strategies to exploit these regulatory mechanisms to suppress immune responses and persist within the host. Targeting these immunosuppressive mechanisms during infection can enhance immune responses and improve infection outcomes. The suppressive mechanisms of regulatory cells are diverse and complex, influenced by the context of the immune response, such as the type of pathogen or tissue involved. These mechanisms include the production of inhibitory cytokines like IL-10 and TGF-β, which inhibit pro-inflammatory cytokines and dampen effector T cell activation. Regulatory cells also utilize inhibitory receptors such as CTLA-4 and PD-1 to suppress effector cell function. Additionally, they modulate metabolic reprogramming in effector immune cells to limit their activation and proliferation. Tregs suppress immune responses through the release of inhibitory cytokines, cytotoxic effects on effector cells, and modulation of antigen-presenting cell function. Bregs contribute to immune regulation by producing IL-10 and modulating T cell differentiation. MDSCs exert strong immunosuppressive activity through arginine metabolism, nitric oxide, reactive oxygen species, and metabolic disruption. Understanding these mechanisms is crucial for developing targeted therapies to modulate immune responses in infectious diseases. The complexity of regulatory networks in infections highlights the need for context-specific approaches to effectively combat pathogens while maintaining immune homeostasis.Regulatory cells, including regulatory T cells (Tregs), regulatory B cells (Bregs), and myeloid-derived suppressor cells (MDSCs), play a critical role in maintaining immune tolerance and controlling immune responses during infections. However, pathogens have evolved strategies to exploit these regulatory mechanisms to suppress immune responses and persist within the host. Targeting these immunosuppressive mechanisms during infection can enhance immune responses and improve infection outcomes. The suppressive mechanisms of regulatory cells are diverse and complex, influenced by the context of the immune response, such as the type of pathogen or tissue involved. These mechanisms include the production of inhibitory cytokines like IL-10 and TGF-β, which inhibit pro-inflammatory cytokines and dampen effector T cell activation. Regulatory cells also utilize inhibitory receptors such as CTLA-4 and PD-1 to suppress effector cell function. Additionally, they modulate metabolic reprogramming in effector immune cells to limit their activation and proliferation. Tregs suppress immune responses through the release of inhibitory cytokines, cytotoxic effects on effector cells, and modulation of antigen-presenting cell function. Bregs contribute to immune regulation by producing IL-10 and modulating T cell differentiation. MDSCs exert strong immunosuppressive activity through arginine metabolism, nitric oxide, reactive oxygen species, and metabolic disruption. Understanding these mechanisms is crucial for developing targeted therapies to modulate immune responses in infectious diseases. The complexity of regulatory networks in infections highlights the need for context-specific approaches to effectively combat pathogens while maintaining immune homeostasis.