title: NK cells kill mycobacteria directly by releasing perforin and granulysin.
abstract: Although the mechanisms underlying the cytotoxic effect of NK cells on tumor cells and intracellular bacteria have been studied extensively, it remains unclear how these cells kill extracellular bacterial pathogens. In this study, we examine how human NK cells kill Mycobacterium kansasii and M.tb. The underlying mechanism is contact dependent and requires two cytolytic proteins: perforin and granulysin. Mycobacteria induce enhanced expression of the cytolytic proteins via activation of the NKG2D/NCR cell-surface receptors and intracellular signaling pathways involving ERK, JNK, and p38 MAPKs. These results suggest that NK cells use similar cellular mechanisms to kill both bacterial pathogens and target host cells. This report reveals a novel role for NK cells, perforin, and granulysin in killing mycobacteria and highlights a potential alternative defense mechanism that the immune system can use against mycobacterial infection.
authors.affiliation: Department of Respiratory Therapy, College of Medicine, Fu Jen Catholic University, Taipei, Taiwan;
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Lu
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, and Graduate Institute of Clinical Medical Sciences and.
authors.forename: Ting-Shu
authors.initials: TS
authors.lastname: Wu
authors.affiliation: Departments of Medical Biotechnology and Laboratory Sciences and.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Hsu
authors.affiliation: Microbiology and Immunology, College of Medicine.
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Chang
authors.affiliation: Departments of Medical Biotechnology and Laboratory Sciences and.
authors.forename: Chuan-Sheng
authors.initials: CS
authors.lastname: Lin
authors.affiliation: Department of Clinical Pathology, Linkou Chang Gung Memorial Hospital, Kweishan, Taiwan;
authors.forename: Ju-Hsin
authors.initials: JH
authors.lastname: Chia
authors.affiliation: Department of Clinical Pathology, Linkou Chang Gung Memorial Hospital, Kweishan, Taiwan;
authors.forename: Tsu-Lan
authors.initials: TL
authors.lastname: Wu
authors.affiliation: Departments of Medical Biotechnology and Laboratory Sciences and Research Center of Bacterial Pathogenesis, and Center for Molecular and Clinical Immunology, Chang Gung University, Kweishan, Taiwan;
authors.forename: Tsung-Teng
authors.initials: TT
authors.lastname: Huang
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Kweishan, Taiwan;
authors.forename: Jan
authors.initials: J
authors.lastname: Martel
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Kweishan, Taiwan; Health Sciences Research Institute and Department of Molecular Cell Biology, University of California, Merced, California, USA;
authors.forename: David M
authors.initials: DM
authors.lastname: Ojcius
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Kweishan, Taiwan; Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York, USA; and Biochemical Engineering Research Center, Ming Chi University of Technology, Taipei, Taiwan dingeyoung@hotmail.com hclai@mail.cgu.edu.tw.
authors.forename: John D
authors.initials: JD
authors.lastname: Young
authors.affiliation: Departments of Medical Biotechnology and Laboratory Sciences and Research Center of Bacterial Pathogenesis, and Center for Molecular and Clinical Immunology, Chang Gung University, Kweishan, Taiwan; dingeyoung@hotmail.com hclai@mail.cgu.edu.tw.
authors.forename: Hsin-Chih
authors.initials: HC
authors.lastname: Lai
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D001433:Bacteriolysis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002473:Cell Wall / Q000187:drug effects; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D019909:Mycobacterium kansasii; D009169:Mycobacterium tuberculosis; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D043942:Nanotubes; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D054353:Perforin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C075005:GNLY protein, human; C527085:KLRK1 protein, human; C112837:NCR2 protein, human; C431710:NCR3 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055629:Natural Cytotoxicity Triggering Receptor 2; D055628:Natural Cytotoxicity Triggering Receptor 3; C510468:PRF1 protein, human; D034741:RNA, Small Interfering; D054353:Perforin
keywords: NCR; NKG2D; antibacterial activity; innate immunity; tuberculosis