{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T23:40:09Z","timestamp":1751499609810,"version":"3.41.0"},"reference-count":28,"publisher":"Scientific Scholar","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,8]]},"abstract":"\n Background & objectives:<\/jats:title>\n Scrub typhus is a chigger-borne disease caused by Orientia tsutsugamushi<\/jats:italic>. The immunological reactions to O. tsutsugamushi<\/jats:italic> infection are not completely understood. In this study, we investigated the response of dendritic cells (DCs) to a major 56-kDa scrub typhus antigen Sta56.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n Monocyte-derived human DCs were incubated with different concentrations of recombinant Sta56 and analyzed for maturation based on phagocytic capacity, the ability to induce T-cell proliferation, expression of surface markers, cytokine secretion and activation of toll-like receptor (TLR)-dependent signalling pathways.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n Treatment of DCs with Sta56 induced cell surface expression of CD80, CD83, CD86 and MHC Class II increased the production of interleukin-12 (IL-12) p40, IL-12 p70 and IL-10 and decreased DC phagocytic capacity. Furthermore, Sta56 increased the ability of DCs to activate T-cell proliferation and interferon-\u03b3 secretion. TLR4-specific antibodies neutralized Sta56-elicited effects on DC maturation, suggesting direct interaction between Sta56 and TLR4. Moreover, Sta56 activated nuclear factor (NF)-\u03baB and p38 mitogen-activated protein kinase (MAPK) signalling as evidenced by decrease in Sta56-induced cytokine production and surface marker expression by specific inhibitors helenalin and SB203580, respectively, and increase in I\u03baB\u03b1 and p38 phosphorylation and NF-\u03baB-DNA binding.<\/jats:p>\n <\/jats:sec>\n \n Interpretation & conclusions:<\/jats:title>\n Our results showed that the surface antigen of O. tsutsugamushi<\/jats:italic> activated DCs through interaction with TLR4 and activation of MAPK and NF-\u03baB signalling, suggesting Sta56 as a potential candidate molecule for the development of vaccine against scrub typhus.<\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/ijmr.ijmr_1417_16","type":"journal-article","created":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T04:55:27Z","timestamp":1539924927000},"page":"215-224","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["A surface antigen of Orientia tsutsugamushi activates human monocyte-derived dendritic cells via nuclear factor-kB & p38 mitogen-activated protein kinase pathways"],"prefix":"10.25259","volume":"148","author":[{"given":"Rong-Hwa","family":"Jan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Jung","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ren","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Li","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Kuang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"10894","reference":[{"key":"R1-13-20241212","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.3201\/eid1507.080399","article-title":"Rapid increase of scrub typhus, South Korea, 2001-2006","volume":"15","author":"Kweon","year":"2009","journal-title":"Emerg Infect Dis"},{"key":"R2-13-20241212","doi-asserted-by":"crossref","first-page":"235","DOI":"10.7883\/yoken.JJID.2006.235","article-title":"Epidemiology of scrub typhus in Eastern Taiwan, 2000-2004","volume":"59","author":"Lee","year":"2006","journal-title":"Jpn J Infect Dis"},{"key":"R3-13-20241212","doi-asserted-by":"crossref","first-page":"4772","DOI":"10.1128\/IAI.71.8.4772-4779.2003","article-title":"Recombinant 56-kilodalton major outer membrane protein antigen of Orientia tsutsugamushi Shanxi and its antigenicity","volume":"71","author":"Chen","year":"2003","journal-title":"Infect Immun"},{"key":"R4-13-20241212","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1128\/CDLI.5.4.519-526.1998","article-title":"Expression and refolding of truncated recombinant major outer membrane protein antigen (r56) of Orientia tsutsugamushi and its use in enzyme-linked immunosorbent assays","volume":"5","author":"Ching","year":"1998","journal-title":"Clin Diagn Lab Immunol"},{"key":"R5-13-20241212","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1128\/iai.65.4.1541-1545.1997","article-title":"Induction of homologous immune response to Rickettsia tsutsugamushi Boryong with a partial 56-kilodalton recombinant antigen fused with the maltose-binding protein MBP-bor56","volume":"65","author":"Seong","year":"1997","journal-title":"Infect Immun"},{"key":"R6-13-20241212","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1128\/iai.61.5.1674-1681.1993","article-title":"Murine T-cell response to native and recombinant protein antigens of Rickettsia tsutsugamushi","volume":"61","author":"Hickman","year":"1993","journal-title":"Infect Immun"},{"key":"R7-13-20241212","doi-asserted-by":"crossref","first-page":"458","DOI":"10.4269\/ajtmh.2005.72.458","article-title":"Induction of protective immunity against scrub typhus with a 56-kilodalton recombinant antigen fused with a 47-kilodalton antigen of Orientia tsutsugamushi Karp","volume":"72","author":"Yu","year":"2005","journal-title":"Am J Trop Med Hyg"},{"key":"R8-13-20241212","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1146\/annurev.immunol.18.1.767","article-title":"Immunobiology of dendritic cells","volume":"18","author":"Banchereau","year":"2000","journal-title":"Annu Rev Immunol"},{"key":"R9-13-20241212","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/S0952-7915(97)80153-7","article-title":"Origin, maturation and antigen presenting function of dendritic cells","volume":"9","author":"Cella","year":"1997","journal-title":"Curr Opin Immunol"},{"key":"R10-13-20241212","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1084\/jem.20021908","article-title":"Flexibility of mouse classical and plasmacytoid-derived dendritic cells in directing T helper type 1 and 2 cell development: Dependency on antigen dose and differential toll-like receptor ligation","volume":"197","author":"Boonstra","year":"2003","journal-title":"J Exp Med"},{"key":"R11-13-20241212","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/42030","article-title":"Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells","volume":"388","author":"Cella","year":"1997","journal-title":"Nature"},{"key":"R12-13-20241212","doi-asserted-by":"crossref","first-page":"5491","DOI":"10.4049\/jimmunol.168.11.5491","article-title":"CD40 ligation conditions dendritic cell antigen-presenting function through sustained activation of NF-kappaB","volume":"168","author":"O\u2019Sullivan","year":"2002","journal-title":"J Immunol"},{"key":"R13-13-20241212","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.4049\/jimmunol.162.7.3865","article-title":"Extracellular signal-regulated kinase, stress-activated protein kinase\/c-Jun N-terminal kinase, and p38mapk are involved in IL-10-mediated selective repression of TNF-alpha-induced activation and maturation of human peripheral blood monocyte-derived dendritic cells","volume":"162","author":"Sato","year":"1999","journal-title":"J Immunol"},{"key":"R14-13-20241212","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1182\/blood.V96.3.1039","article-title":"The PI3 kinase, p38 SAP kinase, and NF-kappaB signal transduction pathways are involved in the survival and maturation of lipopolysaccharide-stimulated human monocyte-derived dendritic cells","volume":"96","author":"Ardeshna","year":"2000","journal-title":"Blood"},{"key":"R15-13-20241212","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S0952-7915(02)00365-5","article-title":"How dendritic cells and microbes interact to elicit or subvert protective immune responses","volume":"14","author":"Palucka","year":"2002","journal-title":"Curr Opin Immunol"},{"key":"R16-13-20241212","first-page":"75","article-title":"Molecular characterization of three major outer membrane proteins, TSA56, TSA47 and TSA22, in Orientia tsutsugamushi","volume":"30","author":"Lin","year":"2012","journal-title":"Int J Mol Med"},{"key":"R18-13-20241212","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/j.1348-0421.2012.00496.x","article-title":"Hepatitis B virus surface antigen can activate human monocyte-derived dendritic cells by nuclear factor kappa B and p38 mitogen-activated protein kinase mediated signaling","volume":"56","author":"Jan","year":"2012","journal-title":"Microbiol Immunol"},{"key":"R19-13-20241212","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1146\/annurev.immunol.16.1.225","article-title":"NF-kappa B and rel proteins: Evolutionarily conserved mediators of immune responses","volume":"16","author":"Ghosh","year":"1998","journal-title":"Annu Rev Immunol"},{"key":"R20-13-20241212","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1016\/j.fct.2012.03.066","article-title":"Modulation of oxidative stress by \u03b3-glutamylcysteine (GGC) and conjugated linoleic acid (CLA) isomer mixture in human umbilical vein endothelial cells","volume":"50","author":"Nakamura","year":"2012","journal-title":"Food Chem Toxicol"},{"key":"R21-13-20241212","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1086\/519686","article-title":"Rickettsiae-stimulated dendritic cells mediate protection against lethal rickettsial challenge in an animal model of spotted fever rickettsiosis","volume":"196","author":"Jordan","year":"2007","journal-title":"J Infect Dis"},{"key":"R22-13-20241212","doi-asserted-by":"crossref","first-page":"5071","DOI":"10.4049\/jimmunol.154.10.5071","article-title":"Dendritic cells produce IL-12 and direct the development of th1 cells from naive CD4+ T cells","volume":"154","author":"Macatonia","year":"1995","journal-title":"J Immunol"},{"key":"R23-13-20241212","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1189\/jlb.0804481","article-title":"Polysaccharide purified from Ganoderma lucidum induced activation and maturation of human monocyte-derived dendritic cells by the NF-kappaB and p38 mitogen-activated protein kinase pathways","volume":"78","author":"Lin","year":"2005","journal-title":"J Leukoc Biol"},{"key":"R24-13-20241212","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0165-2478(02)00230-4","article-title":"The role of dendritic cells in the immune response to Salmonella","volume":"85","author":"Wick","year":"2003","journal-title":"Immunol Lett"},{"key":"R25-13-20241212","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.4049\/jimmunol.177.4.2699","article-title":"Increased levels of soluble CD40L in African tick bite fever: Possible involvement of TLRs in the pathogenic interaction between Rickettsia africae, endothelial cells, and platelets","volume":"177","author":"Dam\u00e5s","year":"2006","journal-title":"J Immunol"},{"key":"R26-13-20241212","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1084\/jem.20051720","article-title":"Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity","volume":"203","author":"Querec","year":"2006","journal-title":"J Exp Med"},{"key":"R27-13-20241212","doi-asserted-by":"crossref","first-page":"3285","DOI":"10.1074\/jbc.273.6.3285","article-title":"P38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways are required for nuclear factor-kappaB p65 transactivation mediated by tumor necrosis factor","volume":"273","author":"Vanden Berghe","year":"1998","journal-title":"J Biol Chem"},{"key":"R28-13-20241212","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.4049\/jimmunol.156.3.1082","article-title":"Molecular cloning and characterization of murine IL-12 genes","volume":"156","author":"Yoshimoto","year":"1996","journal-title":"J Immunol"},{"key":"R29-13-20241212","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/cyto.1995.1001","article-title":"Isolation of the human interleukin 10 promoter. Characterization of the promoter activity in Burkitt's lymphoma cell lines","volume":"7","author":"Kube","year":"1995","journal-title":"Cytokine"}],"container-title":["Indian Journal of Medical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/02223309-201848020-00013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T23:00:38Z","timestamp":1751497238000},"score":1,"resource":{"primary":{"URL":"https:\/\/ijmr.org.in\/a-surface-antigen-of-orientia-tsutsugamushi-activates-human-monocyte-derived-dendritic-cells-via-nuclear-factor-kb-p38-mitogen-activated-protein-kinase-pathways\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018]]}},"URL":"https:\/\/doi.org\/10.4103\/ijmr.ijmr_1417_16","relation":{},"ISSN":["0971-5916"],"issn-type":[{"type":"print","value":"0971-5916"}],"subject":[],"published":{"date-parts":[[2018,8]]}}}