Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria
نویسندگان
چکیده
Perforin-2 (MPEG1) is a pore-forming, antibacterial protein with broad-spectrum activity. Perforin-2 is expressed constitutively in phagocytes and inducibly in parenchymal, tissue-forming cells. In vitro, Perforin-2 prevents the intracellular replication and proliferation of bacterial pathogens in these cells. Perforin-2 knockout mice are unable to control the systemic dissemination of methicillin-resistant Staphylococcus aureus (MRSA) or Salmonella typhimurium and perish shortly after epicutaneous or orogastric infection respectively. In contrast, Perforin-2-sufficient littermates clear the infection. Perforin-2 is a transmembrane protein of cytosolic vesicles -derived from multiple organelles- that translocate to and fuse with bacterium containing vesicles. Subsequently, Perforin-2 polymerizes and forms large clusters of 100 Å pores in the bacterial surface with Perforin-2 cleavage products present in bacteria. Perforin-2 is also required for the bactericidal activity of reactive oxygen and nitrogen species and hydrolytic enzymes. Perforin-2 constitutes a novel and apparently essential bactericidal effector molecule of the innate immune system.
منابع مشابه
Perforin - 2 is essential for intracellular defense of parenchymal cells and phagocytes against 1 pathogenic bacteria
19 Perforin-2 (MPEG1) is a pore-forming, antibacterial protein with broad-spectrum activity. Perforin-2 is 20 expressed constitutively in phagocytes and inducibly in parenchymal, tissue-forming cells. In vitro, 21 Perforin-2 prevents the intracellular replication and proliferation of bacterial pathogens in these cells. 22 Perforin-2 knockout mice are unable to control the systemic dissemination...
متن کاملMacrophage defense mechanisms against intracellular bacteria
Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and elimin...
متن کاملCD8+ T Cells Restrict Yersinia pseudotuberculosis Infection: Bypass of Anti-Phagocytosis by Targeting Antigen-Presenting Cells
All Yersinia species target and bind to phagocytic cells, but uptake and destruction of bacteria are prevented by injection of anti-phagocytic Yop proteins into the host cell. Here we provide evidence that CD8(+) T cells, which canonically eliminate intracellular pathogens, are important for restricting Yersinia, even though bacteria are primarily found in an extracellular locale during the cou...
متن کاملInvestigating antimicrobial activity of hydroalcoholic extract and essential oil of Tymbra spicata against some pathogenic bacteria
Introduction: Thymbra spicata (T. spicata) is a conventional medicinal herb which is commonly used in the folklore medicine system of Iran. Aim of the study was to assess the antibacterial activity of the essential oil and hudroalcholic extract of the plant T. spicata on some important bacteria. Materials & methods: The essential oil and extract of T. spicata were obtained by hydrodistillation ...
متن کاملInhibition of intracellular bacterial replication in fibroblasts is dependent on the perforin-like protein (perforin-2) encoded by macrophage-expressed gene 1.
Fibroblasts are known to eliminate intracellular bacteria, but the lethal hit of the bactericidal mechanism has not been defined. We show that primary embryonic and established fibroblasts can be induced by interferons or by intracellular bacterial infection to express a perforin-like mRNA previously described as macrophage-expressed gene 1 (Mpeg1). The presence and level of the perforin-like m...
متن کامل