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Since gene expression of perforin and granzymes A and B (GzmA and GzmB), cytolytic proteins linked to CD8<jats:sup>+<\/jats:sup>cell effector function, was enhanced in infected liver tissue, B6 mice deficient in these granular proteins were used to gauge host defense roles. Neither perforin nor GzmA was required; however, mice deficient in GzmB (GzmB<jats:sup>\u2212\/\u2212<\/jats:sup>, GzmB cluster<jats:sup>\u2212\/\u2212<\/jats:sup>, and GzmA\u00d7B cluster double knockout [DKO] mice) showed both delayed granuloma assembly and initially impaired control of parasite replication. Since these two defects in B6 mice were limited to early-stage infection, innately resistant 129\/Sv mice were also tested. In this genetic setting, expression of both innate and subsequent T (Th1) cell-dependent acquired resistance, including the self-cure phenotype, was entirely derailed in GzmA\u00d7B cluster DKO mice. These results, in susceptible B6 mice for GzmB and in resistant 129\/Sv mice for GzmA and\/or the GzmB cluster, point to granzyme-mediated host defense regulation in the liver in experimental visceral leishmaniasis.<\/jats:p>","DOI":"10.1128\/iai.02418-14","type":"journal-article","created":{"date-parts":[[2014,12,2]],"date-time":"2014-12-02T08:05:56Z","timestamp":1417507556000},"page":"702-712","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Granzyme-Mediated Regulation of Host Defense in the Liver in Experimental Leishmania donovani Infection"],"prefix":"10.1128","volume":"83","author":[{"given":"Henry W.","family":"Murray","sequence":"first","affiliation":[{"name":"Department of Medicine, Weill Cornell Medical College, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Mitchell-Flack","sequence":"additional","affiliation":[{"name":"Department of Medicine, Weill Cornell Medical College, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zheng","sequence":"additional","affiliation":[{"name":"Shanghai Jiaotong University School of Life Science and Biotechnology, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA"},{"name":"Shanghai Jiaotong University School of Life Science and Biotechnology, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.8.4916"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2.2.279"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.1.288-293.2000"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2004.00188.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2004.11.002"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.icb7100011"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040704"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.8.4804-4807.2003"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir080"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2613.2001.00199.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000805"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00251"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.11.6284-6293.2002"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050013"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.7.3903-3911.2005"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00490-08"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01468-12"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00383-13"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902762"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002951"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003334"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.4.741"},{"key":"e_1_3_3_24_2","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.4049\/jimmunol.140.11.3971","article-title":"Role of L3T4+ and Lyt2+ cells in experimental visceral leishmaniasis","volume":"140","author":"Stern JJ","year":"1988","unstructured":"Stern JJ, Oca MJ, Rubin BY, Anderson SK, Murray HW. 1988. 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