Cholesterol-dependent cytolysins (CDCs) are key virulence factors involved in many lethal bacterial infections, including pneumonia, necrotizing soft tissue infections, bacterial meningitis, and miscarriage. Host responses to these diseases involve myeloid cells, especially macrophages. Macrophages use several systems to detect and respond to cholesterol-dependent cytolysins, including membrane repair, mitogen-activated protein (MAP) kinase signaling, phagocytosis, cytokine production, and activation of the adaptive immune system. However, CDCs also promote immune evasion by silencing and/or destroying myeloid cells. While there are many common themes between the various CDCs, each CDC also possesses specific features to optimally benefit the pathogen producing it. This review highlights host responses to CDC pathogenesis with a focus on macrophages. Due to their robust plasticity, macrophages play key roles in the outcome of bacterial infections. Understanding the unique features and differences within the common theme of CDCs bolsters new tools for research and therapy.
Keywords: Clostridium perfringens; Streptococcus pyogenes; perfringolysin O; pore-forming toxin; streptolysin O.