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A type III secretion system effector known as YopJ in<jats:italic>Y. pseudotuberculosis<\/jats:italic>and<jats:italic>Y. pestis<\/jats:italic>and YopP in<jats:italic>Y. enterocolitica<\/jats:italic>has been shown to regulate host immune responses to live<jats:italic>Yersinia<\/jats:italic>vaccines. YopJ\/P kills macrophages and dendritic cells, reduces their production of tumor necrosis factor alpha (TNF-\u03b1) and interleukin-12 (IL-12), and promotes systemic colonization in mouse models of intestinal<jats:italic>Yersinia<\/jats:italic>infection. Furthermore, YopP activity decreases antigen presentation by dendritic cells, and a<jats:italic>yopP<\/jats:italic>mutant of a live<jats:italic>Y. enterocolitica<\/jats:italic>carrier vaccine elicited effective priming of CD8 T cells to a heterologous antigen in mice. These results suggest that YopJ\/P activity suppresses both innate and adaptive immune responses to live<jats:italic>Yersinia<\/jats:italic>vaccines. Here, a sublethal intragastric mouse infection model using wild-type and catalytically inactive<jats:italic>yopJ<\/jats:italic>mutant strains of<jats:italic>Y. pseudotuberculosis<\/jats:italic>was developed to further investigate how YopJ action impacts innate and adaptive immune responses to a live vaccine. Surprisingly, YopJ-promoted cytotoxicity and systemic colonization were associated with significant increases in neutrophils in spleens and the proinflammatory cytokines IL-18 and gamma interferon (IFN-\u03b3) in serum samples of mice vaccinated with<jats:italic>Y. pseudotuberculosis<\/jats:italic>. Secretion of IL-18 accompanied YopJ-mediated killing of macrophages infected<jats:italic>ex vivo<\/jats:italic>with<jats:italic>Y. pseudotuberculosis<\/jats:italic>, suggesting a mechanism by which this effector directly increases proinflammatory cytokine levels<jats:italic>in vivo<\/jats:italic>. Mice vaccinated with the wild-type strain or the<jats:italic>yopJ<\/jats:italic>mutant produced similar levels of antibodies to<jats:italic>Y. pseudotuberculosis<\/jats:italic>antigens and were equally resistant to lethal intravenous challenge with<jats:italic>Y. pestis.<\/jats:italic>The findings indicate that a proinflammatory, rather than anti-inflammatory, process accompanies YopJ-promoted cytotoxicity, leading to increased systemic colonization by<jats:italic>Y. pseudotuberculosis<\/jats:italic>and potentially enhancing adaptive immunity to a live vaccine.<\/jats:p>","DOI":"10.1128\/iai.00094-10","type":"journal-article","created":{"date-parts":[[2010,3,16]],"date-time":"2010-03-16T03:54:57Z","timestamp":1268711697000},"page":"2329-2341","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["YopJ-Promoted Cytotoxicity and Systemic Colonization Are Associated with High Levels of Murine Interleukin-18, Gamma Interferon, and Neutrophils in a Live Vaccine Model of<i>Yersinia pseudotuberculosis<\/i>Infection"],"prefix":"10.1128","volume":"78","author":[{"given":"Yue","family":"Zhang","sequence":"first","affiliation":[{"name":"Center for Infectious Diseases and Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11794-5222"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James B.","family":"Bliska","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11794-5222"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)00051-5"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01497-06"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2007.07.010"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00800.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.10.016"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060905"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000573"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.5.1878-1884.1998"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000067"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05871.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.7.3673-3681.2003"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00137-07"},{"key":"e_1_3_2_14_2","first-page":"89","volume":"264","year":"2002","unstructured":"Carniel, E. 2002. 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