{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:42:38Z","timestamp":1777984958616,"version":"3.51.4"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2015,9,3]],"date-time":"2015-09-03T00:00:00Z","timestamp":1441238400000},"content-version":"vor","delay-in-days":44,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Council of Scientific and Industrial Research and the J. C. Bose Fellowship (Department of Science and Technology), Government of India","award":["Network Project Grant BSC 0206 and Supra Institutional Project Grant BSC 0114"],"award-info":[{"award-number":["Network Project Grant BSC 0206 and Supra Institutional Project Grant BSC 0114"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>Intramacrophage protozoan parasite <jats:italic>Leishmania donovani<\/jats:italic>, causative agent of visceral leishmaniasis, escapes Toll\u2010like receptor (TLR) dependent early host immune response by inducing the deubiquitinating enzyme A20, which is sustained up to 6 h postinfection only. Therefore, <jats:italic>Leishmania<\/jats:italic> must apply other means to deactivate late host responses. Here, we elucidated the role of IL\u20101 receptor\u2010associated kinase M (IRAK\u2010M), a negative regulator of TLR signaling, in downregulating macrophage proinflammatory response during late hours of in vitro infection. Our data reveal a sharp decline in IRAK1 and IRAK4 phosphorylation at 24 h postinfection along with markedly reduced association of IRAK1\u2013TNF receptor associated factor 6, which is mandatory for TLR activation. In contrast, IRAK\u2010M was induced after A20 levels decreased and reached a maximum at 24 h postinfection. IRAK\u2010M induction coincided with increased stimulation of TGF\u2010\u03b2, a hallmark cytokine of visceral infection. TGF\u2010\u03b2\u2010dependent signaling\u2010mediated induction of SMAD family of proteins, 2, 3, and 4 plays important roles in transcriptional upregulation of IRAK\u2010M. In infected macrophages, siRNA\u2010mediated silencing of IRAK\u2010M displayed enhanced IRAK1 and IRAK4 phosphorylation with a concomitant increase in downstream NF\u2010\u03baB activity and reduced parasite survival. Taken together, the results suggest that IRAK\u2010M may be targeted by <jats:italic>L. donovani<\/jats:italic> to inhibit TLR\u2010mediated proinflammatory response late during in vitro infection.<\/jats:p>","DOI":"10.1002\/eji.201445336","type":"journal-article","created":{"date-parts":[[2015,7,3]],"date-time":"2015-07-03T15:58:21Z","timestamp":1435939101000},"page":"2787-2797","source":"Crossref","is-referenced-by-count":21,"title":["IRAK\u2010M regulates the inhibition of TLR\u2010mediated macrophage immune response during late in vitro <i>Leishmania donovani<\/i> infection"],"prefix":"10.1002","volume":"45","author":[{"given":"Supriya","family":"Srivastav","sequence":"first","affiliation":[{"name":"Infectious Diseases and Immunology Division CSIR\u2010Indian Institute of Chemical Biology  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amrita","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Calcutta  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayita","family":"Barua","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Calcutta  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"}]},{"given":"Pijush K.","family":"Das","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunology Division CSIR\u2010Indian Institute of Chemical Biology  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,7,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2004.08.009"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2007.12.005"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03741.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1391"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.03.012"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1630"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102845"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00827-9"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2014.513"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001906"},{"key":"e_1_2_7_12_1","first-page":"2532","article-title":"Sepsis\u2010induced suppression of lung innate immunity is mediated by IRAK\u2010M","volume":"116","author":"Deng J. 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