Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria
Ryan M McCormack,
Lesley R de Armas,
Motoaki Shiratsuchi,
Desiree G Fiorentino,
Melissa L Olsson,
Mathias G Lichtenheld,
Alejo Morales,
Kirill Lyapichev,
Louis E Gonzalez,
Natasa Strbo,
Neelima Sukumar,
Olivera Stojadinovic,
Gregory V Plano,
George P Munson,
Marjana Tomic-Canic,
Robert S Kirsner,
David G Russell,
Eckhard R Podack
Affiliations
Ryan M McCormack
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States
Lesley R de Armas
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States
Motoaki Shiratsuchi
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States
Desiree G Fiorentino
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States
Melissa L Olsson
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States
Mathias G Lichtenheld
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States
Alejo Morales
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States
Kirill Lyapichev
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States
Louis E Gonzalez
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States
Natasa Strbo
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States
Neelima Sukumar
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, United States
Olivera Stojadinovic
Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, United States
Gregory V Plano
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States
Marjana Tomic-Canic
Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, United States
Robert S Kirsner
Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Miami, United States
David G Russell
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, United States
Eckhard R Podack
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, United States
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.
