{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:53:20Z","timestamp":1791276800430,"version":"4.1.0"},"reference-count":57,"publisher":"Microbiology Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,7,1]]},"abstract":"<jats:p>The Gram-negative intracellular bacteria<jats:italic>Rickettsia conorii<\/jats:italic>and<jats:italic>Rickettsia typhi<\/jats:italic>are the aetiological agents of Mediterranean spotted fever and endemic typhus, respectively, in humans. Infection of endothelial cells (ECs) lining vessel walls, and the resultant vascular inflammation and haemostatic alterations are salient pathogenetic features of both of these rickettsial diseases. An important consideration, however, is that dramatic differences in the intracellular motility and accumulation patterns for spotted fever versus typhus group rickettsiae have been documented, suggesting the possibility of unique and potentially different interactions with host cells. This study characterized and compared<jats:italic>R. conorii<\/jats:italic>- and<jats:italic>R. typhi<\/jats:italic>-mediated effects on cultured human ECs. The DNA-binding activity of nuclear transcription factor-<jats:italic>\u03ba<\/jats:italic>B (NF-<jats:italic>\u03ba<\/jats:italic>B) and the phosphorylation status of stress-activated p38 kinase were determined as indicators of NF-<jats:italic>\u03ba<\/jats:italic>B and p38 activation.<jats:italic>R. conorii<\/jats:italic>infection resulted in a biphasic activation of NF-<jats:italic>\u03ba<\/jats:italic>B, with an early increase in DNA-binding activity at 3 h, followed by a later peak at 24 h. The activated NF-<jats:italic>\u03ba<\/jats:italic>B species were composed mainly of RelA p65\u2013p50 heterodimers and p50 homodimers.<jats:italic>R. typhi<\/jats:italic>infection of ECs resulted in only early activation of NF-<jats:italic>\u03ba<\/jats:italic>B at 3 h, composed primarily of p65\u2013p50 heterodimers. Whilst<jats:italic>R. conorii<\/jats:italic>infection induced increased phosphorylation of p38 kinase (threefold mean induction) with the maximal response at 3 h, a considerably less-intense response peaking at about 6 h post-infection was found with<jats:italic>R. typhi<\/jats:italic>. Furthermore, mRNA expression of the chemokines interleukin (IL)-8 and monocyte chemoattractant protein-1 in ECs infected with either<jats:italic>Rickettsia<\/jats:italic>species was higher than the corresponding controls, but there were distinct differences in the secretion patterns for IL-8, suggesting the possibility of involvement of post-transcriptional control mechanisms or differences in the release from intracellular storage sites. Thus, the intensity and kinetics of host-cell responses triggered by spotted fever and typhus species exhibit distinct variations that could subsequently lead to differences in the extent of endothelial activation and inflammation and serve as important determinants of pathogenesis.<\/jats:p>","DOI":"10.1099\/jmm.0.47050-0","type":"journal-article","created":{"date-parts":[[2007,6,18]],"date-time":"2007-06-18T22:42:55Z","timestamp":1182206575000},"page":"896-906","source":"Crossref","is-referenced-by-count":22,"title":["Comparative analysis of host-cell signalling mechanisms activated in response to infection with Rickettsia conorii and Rickettsia typhi"],"prefix":"10.1099","volume":"56","author":[{"given":"Elena","family":"Rydkina","sequence":"first","affiliation":[{"name":"Hematology-Oncology Unit, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abha","family":"Sahni","sequence":"additional","affiliation":[{"name":"Hematology-Oncology Unit, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Silverman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev K.","family":"Sahni","sequence":"additional","affiliation":[{"name":"Hematology-Oncology Unit, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1093\/ajcp\/75.2.156","article-title":"The liver in Rocky Mountain spotted fever","volume":"75","author":"Adams","year":"1981","journal-title":"Am J Clin Pathol"},{"key":"R2","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1161\/01.RES.0000204553.32549.a7","article-title":"Mechanisms of endothelial cell heterogeneity in health and disease","volume":"98","author":"Aird","year":"2006","journal-title":"Circ Res"},{"key":"R3","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/24094","article-title":"The genome sequence of Rickettsia prowazekii and the origin of mitochondria","volume":"396","author":"Andersson","year":"1998","journal-title":"Nature"},{"key":"R4","doi-asserted-by":"crossref","first-page":"6261","DOI":"10.1128\/JB.00371-06","article-title":"Study of the five Rickettsia prowazekii proteins annotated as ATP\/ADP translocases (Tlc): only Tlc1 transports ATP\/ADP, while Tlc4 and Tlc5 transport other ribonucleotides","volume":"188","author":"Audia","year":"2006","journal-title":"J Bacteriol"},{"key":"R5","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S0733-8635(05)70439-3","article-title":"Rickettsialpox","volume":"15","author":"Boyd","year":"1997","journal-title":"Dermatol Clin"},{"key":"R6","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1097\/01.dad.0000245198.80847.ff","article-title":"Cutaneous vasculitis update: neutrophilic muscular vessel and eosinophilic, granulomatous, and lymphocytic vasculitis syndromes","volume":"29","author":"Carlson","year":"2007","journal-title":"Am J Dermatopathol"},{"key":"R7","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.ijmm.2005.05.006","article-title":"Expression and secretion of chemotactic cytokines IL-8 and MCP-1 by human endothelial cells after Rickettsia rickettsii infection: regulation by nuclear transcription factor NF- \u03ba B","volume":"295","author":"Clifton","year":"2005","journal-title":"Int J Med Microbiol"},{"key":"R8","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1086\/520353","article-title":"Rickettsia conorii infection enhances vascular cell adhesion molecule-1- and intercellular adhesion molecule-1-dependent mononuclear cell adherence to endothelial cells","volume":"175","author":"Dignat-George","year":"1997","journal-title":"J Infect Dis"},{"key":"R9","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1093\/ajcp\/112.2.159","article-title":"Hemostatic changes in Rocky Mountain spotted fever and Mediterranean spotted fever","volume":"112","author":"Elghetany","year":"1999","journal-title":"Am J Clin Pathol"},{"key":"R10","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/978-1-4757-4580-1_19","article-title":"Interaction of rickettsiae with eukaryotic cells. 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