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In our study,\n                    <jats:italic>Leishmania major<\/jats:italic>\n                    grew normally in RAW cells, RAW\u2010expressing dominant\u2010negative PKR (PKR\u2010DN) cells, and macrophages of PKR\u2010knockout mice, revealing that PKR is dispensable for\n                    <jats:italic>L. major<\/jats:italic>\n                    growth in macrophages. PKR activation in infected macrophages with poly I:C resulted in parasite death. Fifty percent of\n                    <jats:italic>L. major<\/jats:italic>\n                    \u2010knockout lines for the ecotin\u2010like serine peptidase inhibitor (ISP2; \u0394\n                    <jats:italic>isp<\/jats:italic>\n                    2\n                    <jats:italic>\/isp<\/jats:italic>\n                    3), an inhibitor of neutrophil elastase (NE), died in RAW cells or macrophages from 129Sv mice, as a result of PKR activation. Inhibition of PKR or NE or neutralization of Toll\u2010like receptor 4 or 2(TLR4 or TLR2) prevented the death of\n                    <jats:italic>\u0394isp<\/jats:italic>\n                    2\n                    <jats:italic>\/isp<\/jats:italic>\n                    3.\n                    <jats:italic>\u0394isp<\/jats:italic>\n                    2\n                    <jats:italic>\/isp<\/jats:italic>\n                    3 grew normally in RAW\u2010PKR\u2010DN cells or macrophages from 129Sv\n                    <jats:italic>\n                      pkr\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      , tlr2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      , trif\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    , and\n                    <jats:italic>\n                      myd88\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice, associating NE activity, PKR, and TLR responses with parasite death.\n                    <jats:italic>\u0394isp<\/jats:italic>\n                    2\n                    <jats:italic>\/isp<\/jats:italic>\n                    3 increased the expression of mRNA for TNF\u2010\u03b1 by 2\u2010fold and of interferon \u03b2 (IFN\u03b2) in a PKR\u2010dependent manner. Antibodies to TNF\u2010\u03b1 reversed the 95% killing by\n                    <jats:italic>\u0394isp<\/jats:italic>\n                    2\n                    <jats:italic>\/isp<\/jats:italic>\n                    3, whereas they grew normally in macrophages from IFN receptor\u2013knockout mice. We propose that ISP2 prevents the activation of PKR\n                    <jats:italic>via<\/jats:italic>\n                    an NE\u2010TLR4\u2010TLR2 axis to control innate responses that contribute to the killing of\n                    <jats:italic>L. major<\/jats:italic>\n                    .\u2014Faria, M. S., Calegari\u2010Silva, T. C., de Carvalho Vivarini, A., Mottram, J. C., Lopes, U. G., Lima, A. P. C. A. Role of protein kinase R in the killing of\n                    <jats:italic>Leishmania major<\/jats:italic>\n                    by macrophages in response to neutrophil elastase and TLR4\n                    <jats:italic>via<\/jats:italic>\n                    TNF\u03b1 and IFN\u03b2.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 28, 3050\u20133063 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-245126","type":"journal-article","created":{"date-parts":[[2014,4,15]],"date-time":"2014-04-15T00:06:22Z","timestamp":1397520382000},"page":"3050-3063","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Role of protein kinase R in the killing of\n                    <i>Leishmania major<\/i>\n                    by macrophages in response to neutrophil elastase and TLR4\n                    <i>via<\/i>\n                    TNF\u03b1 and IFN\u03b2"],"prefix":"10.1096","volume":"28","author":[{"given":"Marilia S.","family":"Faria","sequence":"first","affiliation":[{"name":"Instituto de Biofisica Carlos Chagas Filho Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tereza C.","family":"Calegari\u2010Silva","sequence":"additional","affiliation":[{"name":"Instituto de Biofisica Carlos Chagas Filho Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aislan de Carvalho","family":"Vivarini","sequence":"additional","affiliation":[{"name":"Instituto de Biofisica Carlos Chagas Filho Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy C.","family":"Mottram","sequence":"additional","affiliation":[{"name":"The Wellcome Trust Centre for Molecular Parasitology Institute of Infection, Immunity, and Inflammation College of Medical, Veterinary, and Life Sciences University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulisses Gazos","family":"Lopes","sequence":"additional","affiliation":[{"name":"Instituto de Biofisica Carlos Chagas Filho Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula C. 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