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However, the role of pattern recognition by host innate receptors in CSP is poorly understood in <jats:italic>Leishmania donovani<\/jats:italic> infection. Here, we have demonstrated that cytosolic targeting of <jats:italic>L.donovani<\/jats:italic> DNA (Ld-DNA) inhibits macrophage responsiveness to IFN\u0263, through decreased MHC-II expression and lowered pSTAT1 (Y701) levels, involving host three-prime repair exonuclease-1 (TREX-1). The Ld-DNA potently induced type-1 IFNs, i.e. significant over-production of IFN\u03b2 through activation of the IRF pathway. Interestingly, knockdown of TRIF or MyD88 expression in macrophages had no effect on cytosolic Ld-DNA transfection-mediated IFN-\u03b2 production, indicating involvement of a TLR independent pathway. Contrastingly, Ld-DNA failed to induce IFN\u03b2 in both TBK-1 and IRF3KO knockout macrophages. Although IFN\u03b2 was not induced by Ld-DNA in STING- knockout macrophages, STING alone was not enough for the induction. Evidently, besides STING, Ld-DNA recognition for induction of IFN\u03b2 critically required cytosolic cyclic GMP-AMP synthase (cGAS). Furthermore, the cGAS dependent targeting of Ld-DNA induced IFN\u03b2 over-production that contributed to antimony resistance in <jats:italic>L.donovani<\/jats:italic> infection. We provide the first evidence that enhanced cytosolic sensing of Ld-DNA in infection by antimony resistant (SBR-LD), but not antimony sensitive <jats:italic>L.donovani<\/jats:italic> strains (SBS-LD), was critically regulated by host MDRs, multi drug resistant associated protein 1 (MRP 1) and permeability glycoprotein (P-gp) in macrophages. Collectively, our results disclose Ld-DNA as a vital pathogen associated molecular pattern (PAMP) driving host Type-I IFN responses and antimony resistance. The findings may help in future development of policies for novel anti-leishmanial therapeutics.<\/jats:p>","DOI":"10.1038\/s41598-019-45800-0","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T10:32:20Z","timestamp":1562581940000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["RETRACTED ARTICLE: Nucleic acid sensing activates the innate cytosolic surveillance pathway and promotes parasite survival in visceral leishmaniasis"],"prefix":"10.1038","volume":"9","author":[{"given":"Sushmita","family":"Das","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashish","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhishek","family":"Mandal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumar","family":"Abhishek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudha","family":"Verma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajay","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pradeep","family":"Das","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,7,8]]},"reference":[{"issue":"12","key":"45800_CR1","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.pt.2006.09.004","volume":"22","author":"J Alvar","year":"2006","unstructured":"Alvar, J., Yactayo, S. & Bern, C. 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