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In this study, we report a detrimental role of Ly6C<jats:sup>hi<\/jats:sup>iMOs in visceral leishmaniasis (VL) caused by<jats:italic>Leishmania donovani<\/jats:italic>. We demonstrate that Ly6C<jats:sup>hi<\/jats:sup>iMOs are continuously recruited into the spleen and liver during<jats:italic>L. donovani<\/jats:italic>infection and they are preferential targets for the parasite. Using microarray-based gene expression profiling, we show that Ly6C<jats:sup>hi<\/jats:sup>iMOs isolated from the infected liver and spleen have distinct phenotypic and activation profiles. Furthermore, we demonstrate that blocking the recruitment of Ly6C<jats:sup>hi<\/jats:sup>iMOs into the liver and spleen during<jats:italic>L. donovani<\/jats:italic>infection using a CCR2 antagonist reduces the frequency of the pathogenic IFN-\u03b3\/IL10 dual producer CD4+ T cells in the spleen and leads to a significant reduction in parasite loads in the liver and spleen. Using STAT1\u2212\/\u2212 mice we show that STAT1 is critical for mediating the recruitment of Ly6C<jats:sup>hi<\/jats:sup>iMOs into organs during<jats:italic>L. donovani<\/jats:italic>infection, and adaptive transfer of wild type Ly6C<jats:sup>hi<\/jats:sup>iMOs into STAT1\u2212\/\u2212 recipients renders them susceptible to disease. Our findings reveal an unexpected pathogenic role for Ly6C<jats:sup>hi<\/jats:sup>iMOs in promoting parasite survival in VL and open the possibility of targeting this population for host-directed therapy during VL.<\/jats:p>","DOI":"10.1038\/s41598-017-14935-3","type":"journal-article","created":{"date-parts":[[2017,10,25]],"date-time":"2017-10-25T14:47:52Z","timestamp":1508942872000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Ly6Chi inflammatory monocytes promote susceptibility to Leishmania donovani infection"],"prefix":"10.1038","volume":"7","author":[{"given":"Cesar","family":"Terrazas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Varikuti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Oghumu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi M.","family":"Steinkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurittin","family":"Ardic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Kimble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hira","family":"Nakhasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhay R.","family":"Satoskar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,10,31]]},"reference":[{"key":"14935_CR1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/B978-0-12-407679-2.00005-3","volume":"82","author":"G Gupta","year":"2013","unstructured":"Gupta, G., Oghumu, S. & Satoskar, A. 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