title: Interleukin-22-Induced Antimicrobial Phospholipase A2 Group IIA Mediates Protective Innate Immunity of Nonhematopoietic Cells against Listeria monocytogenes.
abstract: Listeria monocytogenes is a bacterial pathogen which establishes intracellular parasitism in various cells, including macrophages and nonhematopoietic cells, such as hepatocytes. It has been reported that several proinflammatory cytokines have pivotal roles in innate protection against L. monocytogenes infection. We found that a proinflammatory cytokine, interleukin 22 (IL-22), was expressed by CD3(+) CD4(+) T cells at an early stage of L. monocytogenes infection in mice. To assess the influence of IL-22 on L. monocytogenes infection in hepatocytes, cells of a human hepatocellular carcinoma line, HepG2, were treated with IL-22 before L. monocytogenes infection in vitro. Gene expression analysis of the IL-22-treated HepG2 cells identified phospholipase A2 group IIA (PLA2G2A) as an upregulated antimicrobial molecule. Addition of recombinant PLA2G2A to the HepG2 culture significantly suppressed L. monocytogenes infection. Culture supernatant of the IL-22-treated HepG2 cells contained bactericidal activity against L. monocytogenes, and the activity was abrogated by a specific PLA2G2A inhibitor, demonstrating that HepG2 cells secreted PLA2G2A, which killed extracellular L. monocytogenes. Furthermore, colocalization of PLA2G2A and L. monocytogenes was detected in the IL-22-treated infected HepG2 cells, which suggests involvement of PLA2G2A in the mechanism of intracellular killing of L. monocytogenes by HepG2 cells. These results suggest that IL-22 induced at an early stage of L. monocytogenes infection enhances innate immunity against L. monocytogenes in the liver by stimulating hepatocytes to produce an antimicrobial molecule, PLA2G2A.
authors.affiliation: Molecular Microbiology Group, Department of Infectious Diseases, Tropical Biosphere Research Center, and Department of Host Defense, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Yamato
authors.initials: Y
authors.lastname: Okita
authors.affiliation: Molecular Microbiology Group, Department of Infectious Diseases, Tropical Biosphere Research Center, and Department of Host Defense, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Shiono
authors.affiliation: Molecular Microbiology Group, Department of Infectious Diseases, Tropical Biosphere Research Center, and Department of Host Defense, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Yahagi
authors.affiliation: Molecular Microbiology Group, Department of Infectious Diseases, Tropical Biosphere Research Center, and Department of Host Defense, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Hamada
authors.affiliation: Molecular Microbiology Group, Department of Infectious Diseases, Tropical Biosphere Research Center, and Department of Host Defense, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Umemura
authors.affiliation: Molecular Microbiology Group, Department of Infectious Diseases, Tropical Biosphere Research Center, and Department of Host Defense, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan matsuzak@comb.u-ryukyu.ac.jp.
authors.forename: Goro
authors.identifier: http://orcid.org/0000-0002-6043-739X
authors.initials: G
authors.lastname: Matsuzaki
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D054501:Group II Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008089:Listeria monocytogenes / Q000187:drug effects / Q000276:immunology*; D008088:Listeriosis / Q000201:enzymology / Q000276:immunology*; D008099:Liver / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D000097043:Interleukin-22
chemical_list: D054501:Group II Phospholipases A2; D007378:Interleukins; D000097043:Interleukin-22; C516287:PLA2G2A protein, human