{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T20:57:22Z","timestamp":1767905842488,"version":"3.49.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Severe sepsis and septic shock caused mainly by bacterial infections are life-threatening conditions that urge the development of novel therapies. However, host responses to and pathophysiology of sepsis have not been clearly understood, which remains a major obstacle for the development of effective therapeutics. Recently, we have shown that stimulation of a costimulatory molecule, CD137, enhanced survival of mice infected with the Gram-positive (G\n            <jats:sup>+<\/jats:sup>\n            ) intracellular bacterium\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Listeria monocytogenes<\/jats:named-content>\n            but decreased survival in a polymicrobial sepsis model. Herein, we report that CD137 deficiency or blocking of CD137 signaling decreased antibacterial responses of mice infected with G\n            <jats:sup>+<\/jats:sup>\n            bacteria (\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            ,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Streptococcus pneumoniae<\/jats:named-content>\n            , and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterococcus faecalis<\/jats:named-content>\n            ) but increased these responses in mice infected with Gram-negative (G\n            <jats:sup>\u2212<\/jats:sup>\n            ) bacteria (\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n            ,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:named-content>\n            , and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Salmonella enterica<\/jats:named-content>\n            serovar Typhimurium). Consistent with these findings, stimulation of CD137 by administration of agonistic antibody enhanced responses against G\n            <jats:sup>+<\/jats:sup>\n            bacteria, whereas it decreased these responses against G\n            <jats:sup>\u2212<\/jats:sup>\n            bacteria. Neutrophils were responsible for CD137-mediated opposite roles in control of G\n            <jats:sup>+<\/jats:sup>\n            and G\n            <jats:sup>\u2212<\/jats:sup>\n            bacterial infections. Stimulation of CD137 enhanced activities of neutrophils against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            but decreased these activities against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n            , while CD137 blocking produced opposite results with the stimulation of CD137\n            <jats:italic>in vivo<\/jats:italic>\n            and\n            <jats:italic>in vitro<\/jats:italic>\n            . Furthermore, we found that combined signaling of CD137 and Toll-like receptor 2 (TLR2) induced synergistic production of tumor necrosis factor alpha (TNF-\u03b1) and interleukin-6 (IL-6) by neutrophils, but combined signaling of CD137 and TLR4 did not. Our data strongly suggest that CD137 may play a dual role in sepsis in association with TLRs.\n          <\/jats:p>","DOI":"10.1128\/iai.00115-13","type":"journal-article","created":{"date-parts":[[2013,4,2]],"date-time":"2013-04-02T01:20:58Z","timestamp":1364865658000},"page":"2168-2177","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["CD137 Expressed on Neutrophils Plays Dual Roles in Antibacterial Responses against Gram-Positive and Gram-Negative Bacterial Infections"],"prefix":"10.1128","volume":"81","author":[{"given":"Quang-Tam","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea"},{"name":"Department of Biochemistry, Faculty of Biology, University of Science, Hochiminh City, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thu-Ha T.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong-A.","family":"Ju","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Ulsan University Hospital, University of Ulsan, Ulsan, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yea-Sol","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Hyun","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology &amp; Immunology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Chul","family":"Lee","sequence":"additional","affiliation":[{"name":"Personalized Medicine System R&amp;D Center, Bio-support Co., Ltd., Kwanyang Doosan Venture Digm, Kwanyang-dong, Dongan-gu, Anyang-si, Kyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byoung S.","family":"Kwon","sequence":"additional","affiliation":[{"name":"Immune and Cell Therapy Branch, Division of Cancer Biology, National Cancer Center, Goyang-si, Gyeongi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rina","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, University of Ulsan, Ulsan, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gyu Yeol","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung-Sam","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Ulsan, Ulsan, Republic of 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