{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T11:21:28Z","timestamp":1772277688000,"version":"3.50.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Leishmania donovani infects macrophages, disrupting immune homeostasis. The underlying mechanism that sustains infection remains unresolved. In view of the potential of Wnt5a signaling to support immune homeostasis, we evaluated the interrelationship of Wnt5a signaling and Leishmania donovani infection. Upon infecting macrophages separately with antimony drug\u2013sensitive and \u2013resistant L. donovani, we noted disruption in the steady-state level of Wnt5a. Moreover, inhibition of Wnt5a signaling by small interfering RNA transfection in vitro or by use of inhibitor of Wnt production in vivo led to an increase in cellular parasite load. In contrast, treatment of macrophages with recombinant Wnt5a caused a decrease in the load of antimony-sensitive and -resistant parasites, thus confirming that Wnt5a signaling antagonizes L. donovani infection. Using inhibitors of the Wnt5a signaling intermediates Rac1 and Rho kinase, we demonstrated that Wnt5a-mediated inhibition of parasite infection in macrophages is Rac1\/Rho dependent. Furthermore, phalloidin staining and reactive oxygen species estimation of Wnt5a-treated macrophages suggested that a Wnt5a-Rac\/Rho\u2013mediated decrease in parasite load is associated with an increase in F- actin assembly and NADPH oxidase activity. Moreover, live microscopy of L. donovani\u2013infected macrophages treated with Wnt5a demonstrated increased endosomal\/lysosomal fusions with parasite-containing vacuoles (parasitophorous vacuoles [PV]). An increase in PV\u2013endosomal\/lysosomal fusion accompanied by augmented PV degradation in Wnt5a-treated macrophages was also apparent from transmission electron microscopy of infected cells. Our results suggest that, although L. donovani evades host immune response, at least in part through inhibition of Wnt5a signaling, revamping Wnt5a signaling can inhibit L. donovani infection, irrespective of drug sensitivity or resistance.<\/jats:p>","DOI":"10.4049\/jimmunol.1601927","type":"journal-article","created":{"date-parts":[[2017,6,29]],"date-time":"2017-06-29T00:30:22Z","timestamp":1498696222000},"page":"992-1002","source":"Crossref","is-referenced-by-count":24,"title":["Wnt5a Signaling Promotes Host Defense against <i>Leishmania donovani<\/i> Infection"],"prefix":"10.1093","volume":"199","author":[{"given":"Arijit","family":"Chakraborty","sequence":"first","affiliation":[{"name":"Division of Cancer Biology and Inflammatory Disorder, Council of Scientific and Industrial Research\u2013Indian Institute of Chemical Biology , Jadavpur, Kolkata 700032,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0716-1619","authenticated-orcid":false,"given":"Sony Priya","family":"Kurati","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology and Inflammatory Disorder, Council of Scientific and Industrial Research\u2013Indian Institute of Chemical Biology , Jadavpur, Kolkata 700032,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9154-0787","authenticated-orcid":false,"given":"Sushil K","family":"Mahata","sequence":"additional","affiliation":[{"name":"Department of Medicine, Veterans Affairs San Diego Healthcare System , San Diego, CA 92161"},{"name":"Department of Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shyam","family":"Sundar","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, Banaras Hindu University , Varanasi 221005,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syamal","family":"Roy","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease and Immunology, Council of Scientific and Industrial Research\u2013Indian Institute of Chemical Biology , Jadavpur, Kolkata 700032,","place":["India"]},{"name":"Coochbehar Panchanan Barma University , Cooch Behar, West Bengal 736101,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malini","family":"Sen","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology and Inflammatory Disorder, Council of Scientific and Industrial Research\u2013Indian Institute of Chemical Biology , Jadavpur, Kolkata 700032,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,8,1]]},"reference":[{"key":"2025030614211614700_r1","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/nrmicro2608","article-title":"Leishmaniasis: complexity at the host-pathogen interface","volume":"9","author":"Kaye","year":"2011","journal-title":"Nat. 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