{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T13:58:22Z","timestamp":1754488702328,"version":"3.37.3"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI021242"],"award-info":[{"award-number":["AI021242"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI101413"],"award-info":[{"award-number":["AI101413"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Biodefense Training Grant at the University of Texas Medical Branch","award":["PT32-AI060549"],"award-info":[{"award-number":["PT32-AI060549"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Spotted fever group rickettsiae cause potentially life-threatening infections throughout the world. Several members of the Toll-like receptor (TLR) family are involved in host response to rickettsiae, and yet the mechanisms by which these TLRs mediate host immunity remain incompletely understood. In the present study, we found that host susceptibility of MyD88<jats:sup>\u2212\/\u2212<\/jats:sup>mice to infection with<jats:named-content content-type=\"genus-species\">Rickettsia conorii<\/jats:named-content>or<jats:named-content content-type=\"genus-species\">Rickettsia australis<\/jats:named-content>was significantly greater than in wild-type (WT) mice, in association with severely impaired bacterial clearance<jats:italic>in vivo<\/jats:italic>.<jats:named-content content-type=\"genus-species\">R. australis<\/jats:named-content>-infected MyD88<jats:sup>\u2212\/\u2212<\/jats:sup>mice showed significantly lower expression levels of gamma interferon (IFN-\u03b3), interleukin-6 (IL-6), and IL-1\u03b2, accompanied by significantly fewer inflammatory infiltrates of macrophages and neutrophils in infected tissues, than WT mice. The serum levels of IFN-\u03b3, IL-12, IL-6, and granulocyte colony-stimulating factor were significantly reduced, while monocyte chemoattractant protein 1, macrophage inflammatory protein 1\u03b1, and RANTES were significantly increased in infected MyD88<jats:sup>\u2212\/\u2212<\/jats:sup>mice compared to WT mice. Strikingly,<jats:named-content content-type=\"genus-species\">R. australis<\/jats:named-content>infection was incapable of promoting increased expression of MHC-II<jats:sup>high<\/jats:sup>and production of IL-12p40 in MyD88<jats:sup>\u2212\/\u2212<\/jats:sup>bone marrow-derived dendritic cells (BMDCs) compared to WT BMDCs, although costimulatory molecules were upregulated in both types of BMDCs. Furthermore, the secretion levels of IL-1\u03b2 by<jats:named-content content-type=\"genus-species\">Rickettsia<\/jats:named-content>-infected BMDCs and in the sera of infected mice were significantly reduced in MyD88<jats:sup>\u2212\/\u2212<\/jats:sup>mice compared to WT controls, suggesting that<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>production of IL-1\u03b2 is MyD88 dependent. Taken together, our results suggest that MyD88 signaling mediates instructive signals in DCs and secretion of IL-1\u03b2 and type 1 immune cytokines, which may account for the protective inflammatory response during rickettsial infection.<\/jats:p>","DOI":"10.1128\/iai.01361-15","type":"journal-article","created":{"date-parts":[[2016,1,12]],"date-time":"2016-01-12T03:48:58Z","timestamp":1452570538000},"page":"883-893","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["MyD88 Mediates Instructive Signaling in Dendritic Cells and Protective Inflammatory Response during Rickettsial Infection"],"prefix":"10.1128","volume":"84","author":[{"given":"Jeremy","family":"Bechelli","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Smalley","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Judy","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Valdes","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H.","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"2497","volume-title":"Textbook of pediatric infectious diseases","author":"Edwards MS","year":"2004","unstructured":"Edwards MS, Feigin RD. 2004. Rickettsial diseases, p 2497\u20132515. In Feigin RD, Cherry JD, Demmler GJ, Kaplan SL (ed), Textbook of pediatric infectious diseases, 5th ed. WB Saunders Co, New York, NY.","edition":"5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/518145"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/174.5.1051"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/368415"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.022"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80136-7"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1087262"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80086-2"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni712"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1391"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2231"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00311-08"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1009674"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034062"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.9.5688"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00007-07"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/519686"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00349-09"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.182.3.1609"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-10172"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2009.03.004"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2010.05.004"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/bcr2615"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.03.020"},{"key":"e_1_3_3_27_2","doi-asserted-by":"crossref","first-page":"461","DOI":"10.4049\/jimmunol.70.5.461","article-title":"A toxic substance associated with the rickettsias of the spotted fever group","volume":"70","author":"Bell EJ","year":"1953","unstructured":"Bell EJ, Pickens EG. 1953. A toxic substance associated with the rickettsias of the spotted fever group. J Immunol 70:461\u2013472.","journal-title":"J Immunol"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(03)00301-3"},{"key":"e_1_3_3_29_2","first-page":"1471","article-title":"Rickettsia australis infection: a murine model of a highly invasive vasculopathic rickettsiosis","volume":"142","author":"Feng HM","year":"1993","unstructured":"Feng HM, Wen J, Walker DH. 1993. Rickettsia australis infection: a murine model of a highly invasive vasculopathic rickettsiosis. Am J Pathol 142:1471\u20131482.","journal-title":"Am J Pathol"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1078231"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2005.00317.x"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203024"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011758"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425029"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00092-06"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1246"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.2.1080"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.9.5820"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2005.05.006"},{"key":"e_1_3_3_40_2","volume-title":"Guide for the care and use of laboratory animals","author":"National Research Council","year":"2011","unstructured":"National Research Council. 2011. Guide for the care and use of laboratory animals, 8th ed. National Academies Press, Washington, DC.","edition":"8"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01361-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01361-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T13:04:02Z","timestamp":1692191042000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.01361-15"}},"subtitle":[],"editor":[{"given":"G. H.","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2016,4]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["10.1128\/IAI.01361-15"],"URL":"https:\/\/doi.org\/10.1128\/iai.01361-15","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"type":"print","value":"0019-9567"},{"type":"electronic","value":"1098-5522"}],"subject":[],"published":{"date-parts":[[2016,4]]},"assertion":[{"value":"2015-11-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-12-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-03-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}