{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:29:01Z","timestamp":1791404941286,"version":"4.3.3"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2007,1,1]],"date-time":"2007-01-01T00:00:00Z","timestamp":1167609600000},"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":[[2007,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The discovery that endosymbiotic Wolbachia bacteria play an important role in the pathophysiology of diseases caused by filarial nematodes, including lymphatic filariasis and onchocerciasis (river blindness) has transformed our approach to these disabling diseases. Because these parasites infect hundreds of millions of individuals worldwide, understanding host factors involved in the pathogenesis of filarial-induced diseases is paramount. However, the role of early innate responses to filarial and Wolbachia ligands in the development of filarial diseases has not been fully elucidated. To determine the role of TLRs, we used cell lines transfected with human TLRs and macrophages from TLR and adaptor molecule-deficient mice and evaluated macrophage recruitment in vivo. Extracts of Brugia malayi and Onchocerca volvulus, which contain Wolbachia, directly stimulated human embryonic kidney cells expressing TLR2, but not TLR3 or TLR4. Wolbachia containing filarial extracts stimulated cytokine production in macrophages from C57BL\/6 and TLR4\u2212\/\u2212 mice, but not from TLR2\u2212\/\u2212 or TLR6\u2212\/\u2212 mice. Similarly, macrophages from mice deficient in adaptor molecules Toll\/IL-1R domain-containing adaptor-inducing IFN-\u03b2 and Toll\/IL-1R domain-containing adaptor-inducing IFN-\u03b2-related adaptor molecule produced equivalent cytokines as wild-type cells, whereas responses were absent in macrophages from MyD88\u2212\/\u2212 and Toll\/IL-1R domain-containing adaptor protein (TIRAP)\/MyD88 adaptor-like (Mal) deficient mice. Isolated Wolbachia bacteria demonstrated similar TLR and adaptor molecule requirements. In vivo, macrophage migration to the cornea in response to filarial extracts containing Wolbachia was dependent on TLR2 but not TLR4. These results establish that the innate inflammatory pathways activated by endosymbiotic Wolbachia in B. malayi and O. volvulus filaria are dependent on TLR2-TLR6 interactions and are mediated by adaptor molecules MyD88 and TIRAP\/Mal.<\/jats:p>","DOI":"10.4049\/jimmunol.178.2.1068","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:17:51Z","timestamp":1397848671000},"page":"1068-1076","source":"Crossref","is-referenced-by-count":102,"title":["Innate Immune Responses to Endosymbiotic\n                    <i>Wolbachia<\/i>\n                    Bacteria in\n                    <i>Brugia malayi<\/i>\n                    and\n                    <i>Onchocerca volvulus<\/i>\n                    Are Dependent on TLR2, TLR6, MyD88, and Mal, but Not TLR4, TRIF, or TRAM"],"prefix":"10.1093","volume":"178","author":[{"given":"Amy G","family":"Hise","sequence":"first","affiliation":[{"name":"Center for Global Health and Diseases, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Daehnel","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Illona","family":"Gillette-Ferguson","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun","family":"Cho","sequence":"additional","affiliation":[{"name":"Center for Global Health and Diseases, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen F","family":"McGarry","sequence":"additional","affiliation":[{"name":"Filariasis Research Laboratory, Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine , Liverpool ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J","family":"Taylor","sequence":"additional","affiliation":[{"name":"Filariasis Research Laboratory, Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine , Liverpool ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas T","family":"Golenbock","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease & Immunology, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease & Immunology, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W","family":"Kazura","sequence":"additional","affiliation":[{"name":"Center for Global Health and Diseases, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Pearlman","sequence":"additional","affiliation":[{"name":"Center for Global Health and Diseases, Case Western Reserve University , Cleveland, OH 44106"},{"name":"Department of Ophthalmology, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,1,15]]},"reference":[{"key":"2026012810495755800_R1","volume-title":"Filariasis","year":"2006"},{"key":"2026012810495755800_R2","first-page":"369","volume-title":"Cell. Immunol.","year":"1978"},{"key":"2026012810495755800_R3","first-page":"4313","volume-title":"Infect. Immun.","year":"2001"},{"key":"2026012810495755800_R4","first-page":"1242","volume-title":"Lancet","year":"2000"},{"key":"2026012810495755800_R5","first-page":"215","volume-title":"Vet. Parasitol.","year":"2001"},{"key":"2026012810495755800_R6","first-page":"96","volume-title":"Curr. Microbiol.","year":"2000"},{"key":"2026012810495755800_R7","first-page":"5104","volume-title":"Infect. Immun.","year":"2003"},{"key":"2026012810495755800_R8","first-page":"385","volume-title":"J. Infect. Dis.","year":"2001"},{"key":"2026012810495755800_R9","first-page":"113","volume-title":"Microbes Infect.","year":"2004"},{"key":"2026012810495755800_R10","first-page":"439","volume-title":"Microbes Infect.","year":"2001"},{"key":"2026012810495755800_R11","first-page":"1147","volume-title":"Microbes Infect.","year":"2000"},{"key":"2026012810495755800_R12","first-page":"596","volume-title":"Trans. R Soc. Trop. Med. Hyg.","year":"2000"},{"key":"2026012810495755800_R13","first-page":"467","volume-title":"Parasitology","year":"2004"},{"key":"2026012810495755800_R14","first-page":"413","volume-title":"Immunology","year":"1977"},{"key":"2026012810495755800_R15","first-page":"153","volume-title":"Insect Biochem. Mol. Biol.","year":"1999"},{"key":"2026012810495755800_R16","first-page":"356","volume-title":"Exp. Parasitol.","year":"1999"},{"key":"2026012810495755800_R17","first-page":"1483","volume-title":"J. Infect. Dis.","year":"2005"},{"key":"2026012810495755800_R18","first-page":"1063","volume-title":"Proc. Biol. Sci.","year":"2000"},{"key":"2026012810495755800_R19","first-page":"1415","volume-title":"Lancet","year":"2001"},{"key":"2026012810495755800_R20","first-page":"1081","volume-title":"Clin. Infect. Dis.","year":"2006"},{"key":"2026012810495755800_R21","first-page":"1873","volume-title":"Lancet","year":"2001"},{"key":"2026012810495755800_R22","first-page":"805","volume-title":"J. Infect. Dis.","year":"2002"},{"key":"2026012810495755800_R23","first-page":"663","volume-title":"J. Infect. Dis.","year":"1994"},{"key":"2026012810495755800_R24","first-page":"1071","volume-title":"J. Infect. Dis.","year":"1994"},{"key":"2026012810495755800_R25","first-page":"1429","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2026012810495755800_R26","first-page":"5687","volume-title":"Infect. Immun.","year":"2004"},{"key":"2026012810495755800_R27","first-page":"2442","volume-title":"Infect. Immun.","year":"2006"},{"key":"2026012810495755800_R28","first-page":"1892","volume-title":"Science","year":"2002"},{"key":"2026012810495755800_R29","first-page":"509","volume-title":"Proc. R. Soc. London B. Biol. Sci.","year":"1998"},{"key":"2026012810495755800_R30","first-page":"35489","volume-title":"J. Biol. Chem.","year":"2002"},{"key":"2026012810495755800_R31","first-page":"48122","volume-title":"J. Biol. Chem.","year":"2002"},{"key":"2026012810495755800_R32","first-page":"393","volume-title":"J. Endotoxin Res.","year":"2000"},{"key":"2026012810495755800_R33","first-page":"13766","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2000"},{"key":"2026012810495755800_R34","first-page":"637","volume-title":"Biochem. Soc. Trans.","year":"2003"},{"key":"2026012810495755800_R35","first-page":"743","volume-title":"Nature","year":"2003"},{"key":"2026012810495755800_R36","first-page":"1223","volume-title":"Nat. Immunol.","year":"2003"},{"key":"2026012810495755800_R37","first-page":"53","volume-title":"Med. Microbiol. Immunol.","year":"2003"},{"key":"2026012810495755800_R38","first-page":"8291","volume-title":"Infect. Immun.","year":"2005"},{"key":"2026012810495755800_R39","first-page":"3885","volume-title":"J. Immunol.","year":"2006"},{"key":"2026012810495755800_R40","first-page":"1170","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012810495755800_R41","first-page":"437","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012810495755800_R42","first-page":"57","volume-title":"Mol. Biochem. Parasitol.","year":"2004"},{"key":"2026012810495755800_R43","first-page":"898","volume-title":"J. Infect. Dis.","year":"2001"},{"key":"2026012810495755800_R44","first-page":"940","volume-title":"J. Immunol.","year":"2001"},{"key":"2026012810495755800_R45","first-page":"S63","volume-title":"Parasitology","year":"2005"},{"key":"2026012810495755800_R46","first-page":"2085","volume-title":"Science","year":"1998"},{"key":"2026012810495755800_R47","first-page":"12654","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2001"},{"key":"2026012810495755800_R48","first-page":"1612","volume-title":"Science","year":"1997"},{"key":"2026012810495755800_R49","first-page":"253","volume-title":"Mol. Cell","year":"1998"},{"key":"2026012810495755800_R50","first-page":"473","volume-title":"Cold Spring Harbor Symp. Quant. Biol.","year":"1999"},{"key":"2026012810495755800_R51","first-page":"37227","volume-title":"J. Biol. Chem.","year":"2004"},{"key":"2026012810495755800_R52","first-page":"443","volume-title":"Nature","year":"2002"},{"key":"2026012810495755800_R53","first-page":"78","volume-title":"Nature","year":"2001"},{"key":"2026012810495755800_R54","first-page":"835","volume-title":"Nat. Immunol.","year":"2001"},{"key":"2026012810495755800_R55","first-page":"5874","volume-title":"J. Immunol.","year":"2002"},{"key":"2026012810495755800_R56","first-page":"6668","volume-title":"J. Immunol.","year":"2002"},{"key":"2026012810495755800_R57","first-page":"49751","volume-title":"J. Biol. Chem.","year":"2003"},{"key":"2026012810495755800_R58","first-page":"4304","volume-title":"J. Immunol.","year":"2003"},{"key":"2026012810495755800_R59","first-page":"286","volume-title":"Trends Immunol.","year":"2003"},{"key":"2026012810495755800_R60","first-page":"1144","volume-title":"Nat. Immunol.","year":"2003"},{"key":"2026012810495755800_R61","first-page":"319","volume-title":"Physiol. Genomics","year":"2004"},{"key":"2026012810495755800_R62","first-page":"491","volume-title":"Nat. Immunol.","year":"2003"},{"key":"2026012810495755800_R63","first-page":"225","volume-title":"Ann. Soc. Belg. Med. Trop.","year":"1981"},{"key":"2026012810495755800_R64","first-page":"141","volume-title":"Parasite","year":"1994"},{"key":"2026012810495755800_R65","first-page":"337","volume-title":"Parasitology","year":"1998"},{"key":"2026012810495755800_R66","first-page":"200","volume-title":"Med. Vet. Entomol.","year":"1996"},{"key":"2026012810495755800_R67","first-page":"195","volume-title":"Pathol. Annu.","year":"1980"},{"key":"2026012810495755800_R68","first-page":"1240","volume-title":"J. Immunol.","year":"2006"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/178\/2\/1068\/62658275\/zim00207001068.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/178\/2\/1068\/62658275\/zim00207001068.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:50:05Z","timestamp":1769615405000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/178\/2\/1068\/8023755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,1]]},"references-count":68,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2007,1,15]]},"published-print":{"date-parts":[[2007,1,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.178.2.1068","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2007,1]]},"published":{"date-parts":[[2007,1]]}}}