{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T20:46:32Z","timestamp":1769114792859,"version":"3.49.0"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,1,3]],"date-time":"2014-01-03T00:00:00Z","timestamp":1388707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:p>\n                    Intramacrophage pathogen\n                    <jats:italic>Leishmania donovani<\/jats:italic>\n                    escapes host immune response by subverting Toll\u2010like receptor (TLR) signaling, which is critically regulated by protein ubiquitination. In the present study, we identified tumor necrosis factor receptor\u2010associated factor (TRAF) 3, degradative ubiquitination of which is essential for TLR4 activation, as a target for\n                    <jats:italic>Leishmania<\/jats:italic>\n                    to deactivate LPS\u2010mediated TLR4 signaling. We used LPS\u2010treated RAW 264.7 cells and compared the TLR4\u2010mediated immune response in these cells with\n                    <jats:italic>L. donovani<\/jats:italic>\n                    and\n                    <jats:italic>L. donovani<\/jats:italic>\n                    + LPS costimulated macrophages. TRAF3, which was ubiquitinated (2.1\u2010fold over control) at lys 48 position and subsequently degraded following LPS treatment, persisted in\n                    <jats:italic>L. donovani<\/jats:italic>\n                    and\n                    <jats:italic>L. donovani<\/jats:italic>\n                    + LPS costimulated cells due to defective lys 48 ubiquitination. Lys 63\u2010linked ubiquitination of upstream proteins in the cascade (cIAP1\/2 and TRAF6), mandatory for TRAF3 degradation, was also reduced postinfection. This may be attributed to reduced association between ubiquitin\u2010conjugating enzyme Ubc13 and TRAF6 during infection. Inhibition of TRAF3 before infection by shRNA in Balb\/c mice showed enhanced IL\u201012 and TNF\u2010\u03b1 (10.8\u2010 and 8.1\u2010fold over infected control) and decreased spleen parasite burden (61.3% suppression,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.001), thereby marking reduction in disease progression. Our findings identified TRAF3 as a novel molecular regulator exploited by\n                    <jats:italic>Leishmania<\/jats:italic>\n                    for successful infection.\u2014Gupta, P., Giri, J., Srivastav, S., Chande, A. G., Mukhopadhyaya, R., Das, P. K., Ukil, A.\n                    <jats:italic>Leishmania donovani<\/jats:italic>\n                    targets tumor necrosis factor receptor\u2010associated factor (TRAF) 3 for impairing TLR4\u2010mediated host response.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    28, 28\u20131756 (1768).\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.13-238428","type":"journal-article","created":{"date-parts":[[2014,1,3]],"date-time":"2014-01-03T20:20:17Z","timestamp":1388780417000},"page":"1756-1768","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["<i>Leishmania donovani<\/i>\n                    targets tumor necrosis factor receptor\u2010associated factor (TRAF) 3 for impairing TLR4\u2010mediated host response"],"prefix":"10.1096","volume":"28","author":[{"given":"Purnima","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Biochemistry University of Calcutta Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayeeta","family":"Giri","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Calcutta Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Supriya","family":"Srivastav","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunology Division, Council of Scientific and Industrial Research (CSIR) Indian Institute of Chemical Biology Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajit G.","family":"Chande","sequence":"additional","affiliation":[{"name":"Virology Laboratory Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) Tata Memorial Centre, Kharghar Navi Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Mukhopadhyaya","sequence":"additional","affiliation":[{"name":"Virology Laboratory Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) Tata Memorial Centre, Kharghar Navi Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pijush K.","family":"Das","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunology Division, Council of Scientific and Industrial Research (CSIR) Indian Institute of Chemical Biology Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anindita","family":"Ukil","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Calcutta Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,1,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M513057200"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00755.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1819"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04369"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04374"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80497-5"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200535079"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.1920-1928.2004"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.8.4237"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01388-10"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102845"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0909644"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"929","DOI":"10.4049\/jimmunol.151.2.929","article-title":"Role and effect of IL\u20102 in experimental visceral leishmaniasis","volume":"151","author":"Murray H. 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