{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:12:02Z","timestamp":1791295922075,"version":"4.1.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2009,12,1]],"date-time":"2009-12-01T00:00:00Z","timestamp":1259625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tumor progression locus 2 (Tpl2, also known as Map3k8 and Cot) is a serine-threonine kinase critical in innate immunity, linking toll-like receptors (TLRs) to TNF production through its activation of ERK. Tpl2\u2212\/\u2212 macrophages have abrogated TNF production but overproduce IL-12 in response to TLR ligands. Despite enhanced IL-12 production, Tpl2\u2212\/\u2212 T cells have impaired IFN-\u03b3 production. Therefore, the role of Tpl2 in a bona fide bacterial infection where all of these cytokines are important in host defense is unclear. To address this issue, we infected Tpl2\u2212\/\u2212 mice with the model pathogen Listeria monocytogenes. We found that Tpl2\u2212\/\u2212 mice infected i.v. with L. monocytogenes had increased pathogen burdens compared with wild-type mice and rapidly succumbed to infection. Enhanced susceptibility correlated with impaired signaling through TLR2 and nucleotide-binding oligomerization domain 2, two receptors previously shown to mediate Listeria recognition. Surprisingly, TNF production in response to infection was not significantly impaired, even though Tpl2 has been implicated in the regulation of TNF. We found that the role of Tpl2 has cell-type specific effects in regulating TNF and transduces signals from some, but not all, pattern recognition receptors (PRR). In contrast to the cell-type- and receptor-specific regulation of TNF, we found that Tpl2 is essential for IL-1\u03b2 production from both macrophages and dendritic cells. These studies implicate Tpl2 as an important mediator for collaboration of pattern recognition receptors with danger-associated molecular patterns to induce TNF and IL-1\u03b2 production and optimal host defense.<\/jats:p>","DOI":"10.4049\/jimmunol.0901336","type":"journal-article","created":{"date-parts":[[2009,11,23]],"date-time":"2009-11-23T22:59:20Z","timestamp":1259017160000},"page":"7984-7993","source":"Crossref","is-referenced-by-count":93,"title":["Tumor Progression Locus 2 (Map3k8) Is Critical for Host Defense against\n                    <i>Listeria monocytogenes<\/i>\n                    and IL-1\u03b2 Production"],"prefix":"10.1093","volume":"183","author":[{"given":"Lisa A","family":"Mielke","sequence":"first","affiliation":[{"name":"Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health Bethesda , MD 20892"},{"name":"The Division of Molecular Medicine, Walter and Eliza Hall Institute of Medical Research , Parkville,","place":["Australia"]},{"name":"The Department of Medical Biology, University of Melbourne , Parkville,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L","family":"Elkins","sequence":"additional","affiliation":[{"name":"Laboratory of Mycobacterial Diseases and Cellular Immunology, Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research\/U.S. Food and Drug Administration , Rockville, MD 20852"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai","family":"Wei","sequence":"additional","affiliation":[{"name":"Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health Bethesda , MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"Starr","sequence":"additional","affiliation":[{"name":"Signal Transduction Laboratory, St Vincent\u2019s Institute , Fitzroy,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip N","family":"Tsichlis","sequence":"additional","affiliation":[{"name":"Molecular Oncology Research Institute, Tufts-New England Medical Center , Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J","family":"O'Shea","sequence":"additional","affiliation":[{"name":"Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health Bethesda , MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy T","family":"Watford","sequence":"additional","affiliation":[{"name":"Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health Bethesda , MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,15]]},"reference":[{"key":"2026012811220796600_R1","first-page":"12","article-title":"When signaling pathways collide: positive and negative regulation of toll-like receptor signal transduction.","volume-title":"Immunity","year":"2008"},{"key":"2026012811220796600_R2","first-page":"783","article-title":"Pathogen recognition and innate immunity.","volume-title":"Cell","year":"2006"},{"key":"2026012811220796600_R3","first-page":"4812","article-title":"Nod2, a Nod1\/Apaf-1 family member that is restricted to monocytes and activates NF-\u03baB.","volume-title":"J. 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