{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:48:02Z","timestamp":1792100882140,"version":"4.4.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["SB\/FT\/LS-310\/2012"],"award-info":[{"award-number":["SB\/FT\/LS-310\/2012"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100024586","name":"Council of Scientific and Industrial Research","doi-asserted-by":"publisher","award":["CSIR NWP BSC0114"],"award-info":[{"award-number":["CSIR NWP BSC0114"]}],"id":[{"id":"10.13039\/501100024586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008605","name":"Indian National Science Academy","doi-asserted-by":"publisher","award":["SP\/YSP\/115\/2015"],"award-info":[{"award-number":["SP\/YSP\/115\/2015"]}],"id":[{"id":"10.13039\/100008605","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Reciprocal changes in histone lysine methylation\/demethylation of M(LPS + IFN-\u03b3)\/M(IL-10) genes is one of the factors that direct macrophage polarization and contribute to host defense\/susceptibility toward infection. Although, histone lysine methyltransferases and lysine demethylases orchestrate these events, their role remains elusive in visceral leishmaniasis, a disease associated with macrophage M(IL-10) polarization. In this study, we observed that L. donovani induced the expression of histone lysine methyltransferases Ash1l, Smyd2, and Ezh2 and histone lysine demethylases Kdm5b and Kdm6b in J774 macrophages and BALB\/c mice. Chromatin immunoprecipitation analysis revealed that L. donovani facilitated H3K36 dimethylation at TNF-\u03b1 promoter by Smyd2 and H3K27 trimethylation at inducible NO synthase promoter by Ezh2 to suppress their expression in macrophages. Furthermore, infection-induced Kdm5b and Kdm6b modulated H3K4 and H3K27 trimethylation at IL-12, TNF-\u03b1, and arginase-1 promoters, respectively, whereas H3K4 trimethylation by Ash1l at IL-10 promoter induced its expression. Analysis of transductional events revealed that HIF-1\u03b1 upregulated Kdm5b and Kdm6b expression, whereas Ash1l and Ezh2 expression were induced by transcription factor MeCP2. Additionally, Smyd2 was induced by c-Myc in infected macrophages. Knockdown of Ash1l, Ezh2, Kdm5b, and Kdm6b by specific small interfering RNA and Vivo-Morpholino, as well as inhibition of Smyd2 by its specific inhibitor, AZ505, led to increased protective proinflammatory response and inhibited amastigote multiplication in infected J774 macrophages and BALB\/c mice, respectively. Collectively, our findings demonstrate that L. donovani exploits specific histone lysine methyltransferases\/demethylases to redirect epigenetic programming of M(LPS + IFN-\u03b3)\/M(IL-10) genes for its successful establishment within the host.<\/jats:p>","DOI":"10.4049\/jimmunol.1900251","type":"journal-article","created":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T19:34:25Z","timestamp":1586547265000},"page":"2762-2778","source":"Crossref","is-referenced-by-count":43,"title":["<i>Leishmania donovani<\/i> Subverts Host Immune Response by Epigenetic Reprogramming of Macrophage M(Lipopolysaccharides + IFN-\u03b3)\/M(IL-10) Polarization"],"prefix":"10.1093","volume":"204","author":[{"given":"Naveen","family":"Parmar","sequence":"first","affiliation":[{"name":"Division of Molecular Parasitology and Immunology, Council of Scientific and Industrial Research\u2013Central Drug Research Institute , Lucknow 226031 ,","place":["India"]},{"name":"Academy of Scientific and Innovative Research , Ghaziabad, Uttar Pradesh 201002 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pragya","family":"Chandrakar","sequence":"additional","affiliation":[{"name":"Division of Molecular Parasitology and Immunology, Council of Scientific and Industrial Research\u2013Central Drug Research Institute , Lucknow 226031 ,","place":["India"]},{"name":"Academy of Scientific and Innovative Research , Ghaziabad, Uttar Pradesh 201002 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9907-539X","authenticated-orcid":false,"given":"Susanta","family":"Kar","sequence":"additional","affiliation":[{"name":"Division of Molecular Parasitology and Immunology, Council of Scientific and Industrial Research\u2013Central Drug Research Institute , Lucknow 226031 ,","place":["India"]},{"name":"Academy of Scientific and Innovative Research , Ghaziabad, Uttar Pradesh 201002 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,15]]},"reference":[{"key":"2025030417511833500_r1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.immuni.2014.06.008","article-title":"Macrophage activation and polarization: nomenclature and experimental guidelines","volume":"41","author":"Murray","year":"2014","journal-title":"Immunity"},{"key":"2025030417511833500_r2","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1002\/eji.201141792","article-title":"Epigenetic control of macrophage polarization","volume":"41","author":"Takeuch","year":"2011","journal-title":"Eur. 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