{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:32:37Z","timestamp":1791549157803,"version":"4.3.4"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"28","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,7,12]]},"abstract":"<jats:p>\n                    The generation of reactive oxygen species (ROS) is inherent to immune responses. ROS are crucially involved in host defense against pathogens by promoting bacterial killing, but also as signaling agents coordinating the production of cytokines. Transient Receptor Potential Melastatin 2 (TRPM2) is a Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -permeable channel gated via binding of ADP-ribose, a metabolite formed under conditions of cellular exposure to ROS. Here, we show that TRPM2-deficient mice are extremely susceptible to infection with\n                    <jats:italic>Listeria monocytogenes (Lm<\/jats:italic>\n                    ), exhibiting an inefficient innate immune response. In a comparison with IFN\u03b3R-deficient mice, TRPM2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice shared similar features of uncontrolled bacterial replication and reduced levels of inducible (i)NOS-expressing monocytes, but had intact IFN\u03b3 responsiveness. In contrast, we found that levels of cytokines IL-12 and IFN\u03b3 were diminished in TRPM2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice following\n                    <jats:italic>Lm<\/jats:italic>\n                    infection, which correlated with their reduced innate activation. Moreover, TRPM2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice displayed a higher degree of susceptibility than IL-12\u2013unresponsive mice, and supplementation with recombinant IFN\u03b3 was sufficient to reverse the unrestrained bacterial growth and ultimately the lethal phenotype of\n                    <jats:italic>Lm<\/jats:italic>\n                    -infected TRPM2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. The severity of listeriosis we observed in TRPM2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice has not been reported for any other ion channel. These findings establish an unsuspected role for ADP-ribose and ROS-mediated cation flux for innate immunity, opening up unique possibilities for immunomodulatory intervention through TRPM2.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1010678108","type":"journal-article","created":{"date-parts":[[2011,6,28]],"date-time":"2011-06-28T05:22:51Z","timestamp":1309238571000},"page":"11578-11583","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":132,"title":["Transient Receptor Potential Melastatin 2 (TRPM2) ion channel is required for innate immunity against\n                    <i>Listeria monocytogenes<\/i>"],"prefix":"10.1073","volume":"108","author":[{"given":"Heather","family":"Knowles","sequence":"first","affiliation":[{"name":"Integrated Department of Immunology, National Jewish Health and University of Colorado, Denver, CO 80206;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin W.","family":"Heizer","sequence":"additional","affiliation":[{"name":"Integrated Department of Immunology, National Jewish Health and University of Colorado, Denver, CO 80206;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Integrated Department of Immunology, National Jewish Health and University of Colorado, Denver, CO 80206;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Chapman","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Technologies, Platform Technologies and Science, GlaxoSmithKline Research and Development, Stevenage SG1 2NY, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol Anne","family":"Ogden","sequence":"additional","affiliation":[{"name":"Innate Immunity Discovery Performance Unit, Immuno-Inflammation, GlaxoSmithKline, Collegeville, PA 19426"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Andreasen","sequence":"additional","affiliation":[{"name":"Integrated Department of Immunology, National Jewish Health and University of Colorado, Denver, CO 80206;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Shapland","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Technologies, Platform Technologies and Science, GlaxoSmithKline Research and Development, Stevenage SG1 2NY, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Kucera","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Technologies, Platform Technologies and Science, GlaxoSmithKline Research and Development, Stevenage SG1 2NY, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Mogan","sequence":"additional","affiliation":[{"name":"Integrated Department of Immunology, National Jewish Health and University of Colorado, Denver, CO 80206;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Humann","sequence":"additional","affiliation":[{"name":"Integrated Department of Immunology, National Jewish Health and University of Colorado, Denver, CO 80206;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurel L.","family":"Lenz","sequence":"additional","affiliation":[{"name":"Integrated Department of Immunology, National Jewish Health and University of Colorado, Denver, CO 80206;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alastair D.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Technologies, Platform Technologies and Science, GlaxoSmithKline Research and Development, Stevenage SG1 2NY, United Kingdom; 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