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CD4+ T cells are main cell type which produces Th1\/2 cytokine in the host upon<jats:italic>Leishmania<\/jats:italic>infection. However, the regulatory mechanism for Th1\/2 production is not well understood. In this study, we co-cultured mice CD4+ T cells with<jats:italic>Leishmania donovani<\/jats:italic>infected and uninfected macrophage for the identification of dysregulated miRNAs in CD4+ T cells by next-generation sequencing. Here, we identified 604 and 613 known miRNAs in CD4+ T cells in control and infected samples respectively and a total of only 503 miRNAs were common in both groups. The expression analysis revealed that 112 miRNAs were up and 96 were down-regulated in infected groups, compared to uninfected control. Nineteen up-regulated and 17 down-regulated miRNAs were statistically significant (p\u2009&lt;\u20090.05), which were validated by qPCR. Further, using<jats:italic>insilco<\/jats:italic>approach, we identified the gene targets of significant miRNAs on the basis of CD4+ T cell biology. Eleven up-regulated miRNAs and 9 down-regulated miRNAs were associated with the cellular immune responses and Th1\/2 dichotomy upon<jats:italic>Leishmania donovani<\/jats:italic>infection. The up-regulated miRNAs targeted transcription factors that promote differentiation of CD4+ T cells towards Th1 phenotype. While down-regulated miRNAs targeted the transcription factors that facilitate differentiation of CD4+ T cells towards Th2 populations. The GO and pathway enrichment analysis also showed that the identified miRNAs target the pathway and genes related to CD4+ T cell biology which plays important role in<jats:italic>Leishmania donovani<\/jats:italic>infection.<\/jats:p>","DOI":"10.1038\/s41598-020-60435-2","type":"journal-article","created":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T11:03:19Z","timestamp":1582714999000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Leishmania donovani infection induce differential miRNA expression in CD4+ T cells"],"prefix":"10.1038","volume":"10","author":[{"given":"Vinod","family":"Kumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushmita","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj","family":"Tiwari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumar","family":"Abhishek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Mandal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjay","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taj","family":"Shafi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanvir","family":"Bamra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh Kumar","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5145-0384","authenticated-orcid":false,"given":"Saravanan","family":"Vijayakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhik","family":"Sen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,26]]},"reference":[{"key":"60435_CR1","doi-asserted-by":"publisher","first-page":"e35671","DOI":"10.1371\/journal.pone.0035671","volume":"7","author":"J Alvar","year":"2012","unstructured":"Alvar, J. et al. 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