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However, the involvement of PKC\u03b8 in host-mediated immune responses to pathogens has not been thoroughly investigated. We tested the consequences of PKC\u03b8 ablation on the host response to infection by<jats:italic>Plasmodium berghei<\/jats:italic>ANKA (PbA). We found that both PKC\u03b8<jats:sup>+\/+<\/jats:sup>and PKC\u03b8<jats:sup>\u2212\/\u2212<\/jats:sup>C57BL\/6J mice are susceptible to infection with PbA. However, despite a similar parasite burden, PKC\u03b8<jats:sup>+\/+<\/jats:sup>mice had an earlier onset of neurological signs, characteristics of experimental cerebral malaria (ECM), resulting in an earlier death. These mice suffered from an early and pronounced splenomegaly with a concomitant increase in the total number of CD4<jats:sup>+<\/jats:sup>splenic T cells. In contrast, a large proportion of PbA-infected PKC\u03b8<jats:sup>\u2212\/\u2212<\/jats:sup>mice overcame the acute phase characterized by neurological symptoms and survived longer than PKC\u03b8<jats:sup>+\/+<\/jats:sup>mice. The partial resistance of PKC\u03b8<jats:sup>\u2212\/\u2212<\/jats:sup>mice to ECM was associated with an impaired production of Th1-type cytokines, including gamma interferon and tumor necrosis factor alpha\/lymphotoxin-\u03b1, which are known to exacerbate symptoms leading to ECM. In addition, PbA infection-induced LFA-1 expression in CD8<jats:sup>+<\/jats:sup>T cells was suppressed in PKC\u03b8-deficient T cells, suggesting a diminished ability to adhere to endothelial cells and sequester in brain microvasculature, which may explain the decrease in neurological symptoms. These data implicate PKC\u03b8 in CD4<jats:sup>+<\/jats:sup>Th1<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T-cell-mediated immune responses during PbA infection that contribute to the development of ECM.<\/jats:p>","DOI":"10.1128\/iai.00465-10","type":"journal-article","created":{"date-parts":[[2010,7,27]],"date-time":"2010-07-27T03:17:12Z","timestamp":1280200632000},"page":"4195-4205","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Protein Kinase C \u03b8 Deficiency Increases Resistance of C57BL\/6J Mice to<i>Plasmodium berghei<\/i>Infection-Induced Cerebral Malaria"],"prefix":"10.1128","volume":"78","author":[{"given":"Ariel","family":"Ohayon","sequence":"first","affiliation":[{"name":"The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences and the Cancer Research Center, Ben Gurion University of the Negev, P.O.B. 653, Beer Sheva 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Golenser","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Hebrew University of Jerusalem, 91120 Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Sinay","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences and the Cancer Research Center, Ben Gurion University of the Negev, P.O.B. 653, Beer Sheva 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ami","family":"Tamir","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences and the Cancer Research Center, Ben Gurion University of the Negev, P.O.B. 653, Beer Sheva 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amnon","family":"Altman","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaakov","family":"Pollack","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences and the Cancer Research Center, Ben Gurion University of the Negev, P.O.B. 653, Beer Sheva 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Isakov","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences and the Cancer Research Center, Ben Gurion University of the Negev, P.O.B. 653, Beer Sheva 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4922(02)02353-X"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(00)01749-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200006)30:6<1646::AID-IMMU1646>3.0.CO;2-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.5.2817-2826.2004"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)53494-3"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.8.5126"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2189"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.11.6369"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2008.01053.x"},{"key":"e_1_3_2_11_2","first-page":"413","year":"2006","unstructured":"Breman, J. 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