{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T07:41:26Z","timestamp":1792222886864,"version":"4.4.0"},"reference-count":55,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,10,4]],"date-time":"2011-10-04T00:00:00Z","timestamp":1317686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:p>Visceral leishmaniasis (VL), caused by <jats:italic>Leishmania donovani<\/jats:italic>, is a major health concern in India. It represents T\u2010helper type 2 (Th2) bias of cytokines in active state and Th1 bias at cure. However, the role of the parasite in regulating Toll\u2010like receptor (TLR)\u2010mediated macrophage activation in VL patients remains elusive. In this report, we demonstrated that later stages of <jats:italic>L. donovani<\/jats:italic> infection rendered tolerance to macrophages, leading to incapability for the production of inflammatory cytokines like tumor necrosis factor (TNF)\u2010\u03b1 and interleukin (IL)\u20101\u03b2 in response to TLR stimulation. Overexpression of transforming growth factor (TGF)\u2010\u03b2<jats:sub>1<\/jats:sub>, but not IL\u201010, resulted in suppressed lipopolysaccharide (LPS)\u2010induced production of TNF\u2010\u03b1 and downregulation of TLR4 expression in <jats:italic>L. donovani<\/jats:italic>\u2010infected macrophages. Recombinant human (rh)TGF\u2010\u03b2<jats:sub>1<\/jats:sub> markedly enhanced tyrosine phosphatase (Src homology region 2 domain\u2010containing phosphatase\u20101) activity, but inhibited IL\u20101 receptor\u2010activated kinase (IRAK)\u20101 activation. Addition of neutralizing TGF\u2010\u03b2<jats:sub>1<\/jats:sub> antibody reversed these effects, and thus suggesting the pivotal role of TGF\u2010\u03b2<jats:sub>1<\/jats:sub> in promoting refractoriness for LPS in macrophages. Surprisingly, the use of a tyrosine phosphatase inhibitor (sodium orthovanadate, Na<jats:sub>3<\/jats:sub>VO<jats:sub>4<\/jats:sub>) promoted IRAK\u20101 activation, confirming the negative inhibitory role of tyrosine phosphatase in macrophage activation. Furthermore, rhTGF\u2010\u03b2<jats:sub>1<\/jats:sub> induced tolerance in infected macrophages by reducing inhibitory protein (I\u03baB\u03b1) degradation in a time\u2010dependent manner. In addition, short interfering RNA studies proved that overexpression of A20 ubiquitin\u2010editing protein complex induced inhibitory activity of TGF\u2010\u03b2<jats:sub>1<\/jats:sub> on LPS\u2010mediated nuclear factor\u2010\u03baB activation. Thus, these findings suggest that TGF\u2010\u03b2<jats:sub>1<\/jats:sub> promotes overexpression of A20 through tyrosine phosphatase activity that ensures transient activation of inflammatory signaling pathways in macrophages in active <jats:italic>L. donovani<\/jats:italic> infection.<\/jats:p>","DOI":"10.1038\/icb.2011.80","type":"journal-article","created":{"date-parts":[[2011,10,4]],"date-time":"2011-10-04T09:47:28Z","timestamp":1317721648000},"page":"640-654","source":"Crossref","is-referenced-by-count":34,"title":["TGF\u2010\u03b2<sub>1<\/sub> re\u2010programs TLR4 signaling in <i>L. donovani<\/i> infection: enhancement of SHP\u20101 and ubiquitin\u2010editing enzyme A20"],"prefix":"10.1111","volume":"90","author":[{"given":"Sushmita","family":"Das","sequence":"first","affiliation":[{"name":"Departments of Molecular Parasitology and Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Indian Council of Medical Research (ICMR), Agamkuan  Patna India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Pandey","sequence":"additional","affiliation":[{"name":"Departments of Molecular Parasitology and Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Indian Council of Medical Research (ICMR), Agamkuan  Patna India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Departments of Molecular Parasitology and Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Indian Council of Medical Research (ICMR), Agamkuan  Patna India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abul H","family":"Sardar","sequence":"additional","affiliation":[{"name":"Departments of Molecular Parasitology and Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Indian Council of Medical Research (ICMR), Agamkuan  Patna India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bidyut","family":"Purkait","sequence":"additional","affiliation":[{"name":"Departments of Molecular Parasitology and Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Indian Council of Medical Research (ICMR), Agamkuan  Patna India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Departments of Molecular Parasitology and Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Indian Council of Medical Research (ICMR), Agamkuan  Patna India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeep","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases, Institute of Global Health, University of New Mexico School of Medicine  Albuquerque NM USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidya N","family":"Ravidas","sequence":"additional","affiliation":[{"name":"Departments of Molecular Parasitology and Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Indian Council of Medical Research (ICMR), Agamkuan  Patna India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syamal","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Indian Institute of Chemical Biology (CSIR), Jadavpur  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharmendra","family":"Singh","sequence":"additional","affiliation":[{"name":"Departments of Molecular Parasitology and Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Indian Council of Medical Research (ICMR), Agamkuan  Patna India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Das","sequence":"additional","affiliation":[{"name":"Departments of Molecular Parasitology and Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Indian Council of Medical Research (ICMR), Agamkuan  Patna India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,10,4]]},"reference":[{"key":"e_1_2_8_1_1","unstructured":"Leishmaniasis fact sheet:http:\/\/www.who.int\/tdr\/diseases\/leish\/diseaseinfo.htm."},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182005008139"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1102-1041"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.154.10.5320"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.6.777"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200610-1436CP"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05836"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2009.05.337"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.7.3476"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/35021228"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1606"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2337"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20031377"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1110"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2004.01.004"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1636092"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00121-5"},{"key":"e_1_2_8_18_1","first-page":"466","article-title":"TGF\u2010b\u2010regulated tyrosine phosphatases induce lymphocyte apoptosis in Leishmania donovani\u2010infected hamsters","volume":"18","author":"Banerjee R","year":"2010","journal-title":"Immunol Cell Biol"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.9.5666"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1385\/IR:35:1:127"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI15719"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00853-05"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1003484"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209210200"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000305"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.34.21540"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201762200"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.4.2736"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.13.6721"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1006\/scel.1993.1038"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.182873"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.3003"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2003.00251.x"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/334260a0"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.09.114"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0211638"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.10.4837"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034509334846"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200111)31:11<3185::AID-IMMU3185>3.0.CO;2-J"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1604"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0409289"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200526037"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni0508-459"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200705200"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.12.6136"},{"key":"e_1_2_8_46_1","doi-asserted-by":"crossref","first-page":"14705","DOI":"10.1016\/S0021-9258(18)77165-2","article-title":"The A20 cDNA induced by tumor necrosis factor \u03ba encodes a novel type of zinc finger protein","volume":"265","author":"Opipari AW","year":"1990","journal-title":"J Biol Chem"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.02.002"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02794"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R800032200"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601301"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.285"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803987"},{"key":"e_1_2_8_53_1","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.4049\/jimmunol.139.9.3118","article-title":"Vaccination against cutaneous leishmaniasis in a murine model. II. Immunologic properties of protective and nonprotective subfractions of soluble promastigote extract","volume":"139","author":"Scott P","year":"1987","journal-title":"J Immunol"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.22.13944"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2008.02076.x"}],"updated-by":[{"DOI":"10.1111\/imcb.12609","type":"retraction","label":"Retraction","source":"retraction-watch","updated":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"record-id":"40927"},{"DOI":"10.1111\/imcb.12609","type":"retraction","label":"Retraction","source":"publisher","updated":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000}}],"container-title":["Immunology &amp; Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Ficb.2011.80","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/icb.2011.80","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1038\/icb.2011.80","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/icb.2011.80","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T22:08:49Z","timestamp":1694038129000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1038\/icb.2011.80"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10,4]]},"references-count":55,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2012,7]]}},"alternative-id":["10.1038\/icb.2011.80"],"URL":"https:\/\/doi.org\/10.1038\/icb.2011.80","archive":["Portico"],"relation":{"retraction":[{"id-type":"doi","id":"10.1111\/imcb.12609","asserted-by":"object"}]},"ISSN":["0818-9641","1440-1711"],"issn-type":[{"value":"0818-9641","type":"print"},{"value":"1440-1711","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10,4]]}}}