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Morgan, induced reactive oxygen species, leading to apoptosis in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania donovani<\/jats:named-content>promastigotes, and also was effective in inhibiting intracellular amastigotes at the 50% inhibitory concentration of 2.5 \u03bcg\/ml. The aim of the present study is to characterize the associated immunomodulatory potentials and cellular activation provided by astrakurkurone, leading to effective antileishmanial activity<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>. Astrakurkurone-mediated antileishmanial activity was evaluated by real-time PCR and flow cytometry. The involvement of Toll-like receptor 9 (TLR9) was studied by<jats:italic>in vitro<\/jats:italic>assay in the presence of a TLR9 agonist and antagonist and by<jats:italic>in silico<\/jats:italic>modeling of a three-dimensional structure of the ectodomain of TLR9 and its interaction with astrakurkurone. Astrakurkurone caused a significant increase in TLR9 expression of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">L. donovani<\/jats:named-content>-infected macrophages along with the activation of proinflammatory responses. The involvement of TLR9 in astrakurkurone-mediated amastigote killing has been evidenced from the fact that a TLR9 agonist (CpG, ODN 1826) in combination with astrakurkurone enhanced the amastigote killing, while a TLR9 antagonist (bafilomycin A1) alone or in combination with astrakurkurone curbed the amastigote killing, which could be further justified by<jats:italic>in silico<\/jats:italic>evidence of docking between mouse TLR9 and astrakurkurone. Astrakurkurone was found to reduce the parasite burden<jats:italic>in vivo<\/jats:italic>by inducing protective cytokines, gamma interferon and interleukin 17. Moreover, astrakurkurone was nontoxic toward peripheral blood mononuclear cells of immunocompromised patients with visceral leishmaniasis. Astrakurkurone, a nontoxic antileishmanial, enhances the immune efficiency of host cells, leading to parasite clearance<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1128\/aac.01943-15","type":"journal-article","created":{"date-parts":[[2016,2,17]],"date-time":"2016-02-17T03:49:32Z","timestamp":1455680972000},"page":"2696-2708","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Successful Therapy of Murine Visceral Leishmaniasis with Astrakurkurone, a Triterpene Isolated from the Mushroom Astraeus hygrometricus, Involves the Induction of Protective Cell-Mediated Immunity and TLR9"],"prefix":"10.1128","volume":"60","author":[{"given":"Suvadip","family":"Mallick","sequence":"first","affiliation":[{"name":"Cellular Immunology and Experimental Therapeutics Laboratory, Department of Zoology, West Bengal State University, Barasat, West Bengal, 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