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The roles of Toll-like receptor 2 (TLR2) and TLR4 in innate recognition of<jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>have not been elucidated. By overexpression of TLR2 or TLR4 in HEK293 cells, we demonstrated that TLR2, but not TLR4, recognizes heat-stable compounds of<jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>that were sensitive to treatment with sodium hydroxide, hydrogen peroxide, and proteinase K. TLR2 was required for the secretion of tumor necrosis factor alpha (TNF-\u03b1) and interleukin-6 (IL-6) by dendritic cells. In an intradermal mouse infection model, TLR2-deficient mice did not show impaired control of bacterial growth or reduced survival. Moreover, after intraperitoneal infection, TLR2-deficient mice were even more resistant to lethal infection than C57BL\/6 wild-type mice, which showed stronger symptoms and lower survival rates during the convalescent phase. Compared to the time of reduction of bacterial loads in TLR2-deficient mice, the reduction of bacterial loads in infected organs was accelerated in wild-type mice. The higher mortality of wild-type mice was associated with increased concentrations of serum alkaline phosphatase but not aspartate aminotransferase. The transcription of mRNA for TNF-\u03b1 and IL-6 decreased more rapidly in peritoneum samples from wild-type mice than in those from TLR2-deficient mice and was therefore not a correlate of increased susceptibility. Thus, although TLR2 is an important mediator of the early inflammatory response, it is dispensable for protective immunity against<jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>. Increased susceptibility to<jats:named-content content-type=\"genus-species\">O. tsutsugamushi<\/jats:named-content>infection in TLR2-competent mice rather suggests a TLR2-related immunopathologic effect.<\/jats:p>","DOI":"10.1128\/iai.00185-16","type":"journal-article","created":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T01:59:21Z","timestamp":1473731961000},"page":"3379-3387","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Toll-Like Receptor 2 Recognizes Orientia tsutsugamushi and Increases Susceptibility to Murine Experimental Scrub Typhus"],"prefix":"10.1128","volume":"84","author":[{"given":"Mohammad","family":"Gharaibeh","sequence":"first","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Hagedorn","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Lilla","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Hauptmann","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Heine","sequence":"additional","affiliation":[{"name":"Research Center Borstel, Division of Innate Immunity, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Fleischer","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany"},{"name":"Institute for Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Keller","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.13-0064"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.09.008"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.09.018"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/41131"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401850"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/09680519010070060901"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/340511"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2131-2139.2004"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63095-7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.10.5392"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1009674"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00311-08"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.11.6187"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040248"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir522"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003064"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(98)00204-X"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830261105"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.6.2089"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2008.02.005"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003096"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-92"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.25.17406"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2005.05029.x"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5428.736"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"6971","DOI":"10.4049\/jimmunol.162.12.6971","article-title":"Cutting edge: cells that carry a null allele for Toll-like receptor 2 are capable of responding to endotoxin","volume":"162","author":"Heine H","year":"1999","unstructured":"Heine H, Kirschning CJ, Lien E, Monks BG, Rothe M, Golenbock DT. 1999. 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