{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T22:35:04Z","timestamp":1768775704605,"version":"3.49.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"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":[[2012,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Our immune system has to constantly strike a balance between activation and inhibition of an inflammatory response to combat invading pathogens and avoid inflammation-induced collateral tissue damage. Toll interleukin-1 receptor 8 (IL-1R-8)\/single Ig domain IL-1R-related molecule (TIR8\/SIGIRR) is an inhibitor of Toll-like receptor (TLR)\/IL-1R signaling, which is predominantly expressed in the kidney. The biological role of renal TIR8 during infection is, however, unknown. We therefore evaluated renal TIR8 expression during<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>pyelonephritis and explored its role in host defense using TIR8<jats:sup>\u2212\/\u2212<\/jats:sup>versus TIR8<jats:sup>+\/+<\/jats:sup>mice. We found that TIR8 protein is abundantly present in the majority of cortical tubular epithelial cells. Pyelonephritis resulted in a significant downregulation of TIR8 mRNA in kidneys of TIR8<jats:sup>+\/+<\/jats:sup>mice. TIR8 inhibited an effective host response against<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>, as indicated by diminished renal bacterial outgrowth and dysfunction in TIR8<jats:sup>\u2212\/\u2212<\/jats:sup>mice. This correlated with increased amounts of circulating and intrarenal neutrophils at the early phase of infection. TIR8<jats:sup>\u2212\/\u2212<\/jats:sup>tubular epithelial cells had increased cytokine\/chemokine production when stimulated with lipopolysaccharide (LPS) or heat-killed<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>, suggesting that TIR8 played an anti-inflammatory role during pathogen stimulation by inhibiting LPS signaling. These data suggest that TIR8 is an important negative regulator of an LPS-mediated inflammatory response in tubular epithelial cells and dampens an effective antibacterial host response during pyelonephritis caused by uropathogenic<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>.<\/jats:p>","DOI":"10.1128\/iai.00422-12","type":"journal-article","created":{"date-parts":[[2012,8,14]],"date-time":"2012-08-14T02:32:10Z","timestamp":1344911530000},"page":"3812-3820","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["The Toll Interleukin-1 Receptor (IL-1R) 8\/Single Ig Domain IL-1R-Related Molecule Modulates the Renal Response to Bacterial Infection"],"prefix":"10.1128","volume":"80","author":[{"given":"Jaklien C.","family":"Leemans","sequence":"first","affiliation":[{"name":"Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loes M.","family":"Butter","sequence":"additional","affiliation":[{"name":"Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwendoline J. D.","family":"Teske","sequence":"additional","affiliation":[{"name":"Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"Stroo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilco P.","family":"Pulskens","sequence":"additional","affiliation":[{"name":"Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandrine","family":"Florquin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.10.4054-4062.1995"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.6.4022"},{"key":"e_1_3_3_4_2","first-page":"441","article-title":"Urinary soluble CD14 mediates human proximal tubular epithelial cell injury induced by LPS","volume":"10","author":"Bussolati B","year":"2002","unstructured":"BussolatiBDavidSCambiVTobiasPSCamussiG. 2002. Urinary soluble CD14 mediates human proximal tubular epithelial cell injury induced by LPS. Int. J. Mol. Med. 10:441\u2013449.","journal-title":"Int. J. Mol. Med."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.7.4773"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1051\/medsci\/200723132"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2006.06.003"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013394"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2005.04.013"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2009.11.022"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(02)01054-9"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02361.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.06.001"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.5.3119"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308680101"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.46.3.839-844.1984"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.1.548"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2010.04254.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2004.03.008"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1203\/pdr.0b013e318030d1f4"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900118"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002293"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22832"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803549"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1086\/322030"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00729.x"},{"key":"e_1_3_3_27_2","first-page":"211","article-title":"Unique pattern of expression and inhibition of IL-1 signaling by the IL-1 receptor family member TIR8\/SIGIRR","volume":"14","author":"Polentarutti N","year":"2003","unstructured":"PolentaruttiN. 2003. Unique pattern of expression and inhibition of IL-1 signaling by the IL-1 receptor family member TIR8\/SIGIRR. Eur. Cytokine Netw. 14:211\u2013218.","journal-title":"Eur. Cytokine Netw."},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003596"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501363200"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2009.03.009"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-3955(05)70551-4"},{"key":"e_1_3_3_32_2","doi-asserted-by":"crossref","first-page":"3475","DOI":"10.4049\/jimmunol.138.10.3475","article-title":"Neutrophil recruitment and bacterial clearance correlated with LPS responsiveness in local gram-negative infection","volume":"138","author":"Shahin RD","year":"1987","unstructured":"ShahinRDEngbergIHagbergLSvanborg EdenC. 1987. Neutrophil recruitment and bacterial clearance correlated with LPS responsiveness in local gram-negative infection. J. Immunol. 138:3475\u20133480.","journal-title":"J. Immunol."},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.10.6252"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019204"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01641692"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1998.0452"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.4.2026"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05695-11"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni968"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.3.1286"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31008"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1990.46"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.02.012"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00422-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00422-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,25]],"date-time":"2023-06-25T09:13:10Z","timestamp":1687684390000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00422-12"}},"subtitle":[],"editor":[{"given":"J. N.","family":"Weiser","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2012,11]]},"references-count":42,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2012,11]]}},"alternative-id":["10.1128\/IAI.00422-12"],"URL":"https:\/\/doi.org\/10.1128\/iai.00422-12","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11]]},"assertion":[{"value":"2012-04-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-08-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-10-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}