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It has been reported that several proinflammatory cytokines have pivotal roles in innate protection against<jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content>infection. We found that a proinflammatory cytokine, interleukin 22 (IL-22), was expressed by CD3<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T cells at an early stage of<jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content>infection in mice. To assess the influence of IL-22 on<jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content>infection in hepatocytes, cells of a human hepatocellular carcinoma line, HepG2, were treated with IL-22 before<jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content>infection<jats:italic>in vitro<\/jats:italic>. 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<jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content>infection. Culture supernatant of the IL-22-treated HepG2 cells contained bactericidal activity against<jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content>, and the activity was abrogated by a specific PLA2G2A inhibitor, demonstrating that HepG2 cells secreted PLA2G2A, which killed extracellular<jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content>. Furthermore, colocalization of PLA2G2A and<jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content>was detected in the IL-22-treated infected HepG2 cells, which suggests involvement of PLA2G2A in the mechanism of intracellular killing of<jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content>by HepG2 cells. These results suggest that IL-22 induced at an early stage of<jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content>infection enhances innate immunity against<jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content>in the liver by stimulating hepatocytes to produce an antimicrobial molecule, PLA2G2A.<\/jats:p>","DOI":"10.1128\/iai.01000-15","type":"journal-article","created":{"date-parts":[[2015,12,8]],"date-time":"2015-12-08T15:05:36Z","timestamp":1449587136000},"page":"573-579","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Interleukin-22-Induced Antimicrobial Phospholipase A2 Group IIA Mediates Protective Innate Immunity of Nonhematopoietic Cells against Listeria monocytogenes"],"prefix":"10.1128","volume":"84","author":[{"given":"Yamato","family":"Okita","sequence":"first","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeru","family":"Shiono","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayano","family":"Yahagi","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Hamada","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Umemura","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6043-739X","authenticated-orcid":false,"given":"Goro","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1995.tb02297.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00933.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.4049\/jimmunol.141.9.3203","article-title":"Cloned L3T4+ T lymphocytes protect mice against Listeria monocytogenes by secreting IFN-\u03b3","volume":"141","author":"Magee DM","year":"1988","unstructured":"Magee DM, Wing EJ. 1988. 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