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Here we have identified how HuR, by inducing extracellular vesicles\u2010mediated export of miRNAs, ensures robust derepression of miRNA\u2010repressed cytokines essential for strong pro\u2010inflammatory response in activated mammalian macrophages.\n                    <jats:italic>Leishmania donovani<\/jats:italic>\n                    , the causative agent of visceral leishmaniasis, on the contrary alters immune response of the host macrophage by a variety of complex mechanisms to promote anti\u2010inflammatory response essential for the survival of the parasite. We have found that during\n                    <jats:italic>Leishmania<\/jats:italic>\n                    infection, the pathogen targets HuR to promote onset of anti\u2010inflammatory response in mammalian macrophages. In infected macrophages,\n                    <jats:italic>Leishmania<\/jats:italic>\n                    also upregulate protein phosphatase 2A that acts on Ago2 protein to keep it in dephosphorylated and miRNA\u2010associated form. This causes robust repression of the miRNA\u2010targeted pro\u2010inflammatory cytokines to establish an anti\u2010inflammatory response in infected macrophages. HuR has an inhibitory effect on protein phosphatase 2A expression, and mathematical modelling of macrophage activation process supports antagonistic miRNA\u2010modulatory roles of HuR and protein phosphatase 2A which mutually balances immune response in macrophage by targeting miRNA function. Supporting this model, ectopic expression of the protein HuR and simultaneous inhibition of protein phosphatase 2A induce strong pro\u2010inflammatory response in the host macrophage to prevent the virulent antimonial drug\u2010sensitive or drug\u2010resistant form of\n                    <jats:italic>L.\u00a0donovani<\/jats:italic>\n                    infection. Thus, HuR can act as a balancing factor of immune responses to curtail the macrophage infection process by the protozoan parasite.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201911011","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T08:18:52Z","timestamp":1581063532000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["MicroRNA exporter HuR clears the internalized pathogens by promoting pro\u2010inflammatory response in infected macrophages"],"prefix":"10.1038","volume":"12","author":[{"given":"Avijit","family":"Goswami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamalika","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anup","family":"Mazumder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satarupa","family":"Ganguly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0361-537X","authenticated-orcid":false,"given":"Ishita","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8644-6016","authenticated-orcid":false,"given":"Saikat","family":"Chakrabarti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syamal","family":"Roy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Sundar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1449-8909","authenticated-orcid":false,"given":"Krishnananda","family":"Chattopadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9697-3824","authenticated-orcid":false,"given":"Suvendra N","family":"Bhattacharyya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,7]]},"reference":[{"key":"BFEMMM201911011_CR1","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1146\/annurev.immunol.17.1.593","volume":"17","author":"A Aderem","year":"1999","unstructured":"Aderem A, Underhill DM (1999) Mechanisms of phagocytosis in macrophages. 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