Abstract
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.
Highlights
Cholesterol-dependent cytolysins (CDCs) are a subset of pore-forming toxins that serve as key virulence factors for a wide range of lethal and opportunistic Gram-positive bacterial pathogens that collectively infect or invade most parts of the human body
Key Contribution: This review focuses on host–pathogen interactions between pathogenic bacteria and their hosts, with a focus on cholesterol-dependent cytolysins and macrophages
CDCs figure prominently in many of these attempts. This review explores both general and specific molecular mechanisms used by CDCs to kill, control, or evade macrophages
Summary
Cholesterol-dependent cytolysins (CDCs) are a subset of pore-forming toxins that serve as key virulence factors for a wide range of lethal and opportunistic Gram-positive bacterial pathogens that collectively infect or invade most parts of the human body. Hosts attempt to eliminate these pathogens with both general and tissue-specific approaches. One common approach that has tissue-specific flexibility is activation and polarization of macrophages. Macrophages coordinate the local tissue response with cytokines and can directly eliminate bacteria through phagocytosis and secretion of reactive oxygen/nitrogen species. They further promote wound repair and restore the tissue to homeostasis. Pathogenic bacteria target macrophages for elimination, reprogramming, or shelter. CDCs figure prominently in many of these attempts. This review explores both general and specific molecular mechanisms used by CDCs to kill, control, or evade macrophages
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