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Following the bite-induced breach of the skin barrier,<jats:italic>Leishmania<\/jats:italic>is known to live and replicate predominantly inside professional phagocytes. Although<jats:italic>Leishmania<\/jats:italic>is also able to infect nonphagocytic cells, nonphagocytic cells support limited parasitic replication for unknown reasons. In this study, we show that nonphagocytic cells possess an intrinsic property to restrict<jats:italic>Leishmania<\/jats:italic>growth. Our study defines a novel role for a family of host defense proteins, the guanylate binding proteins (GBPs), in antileishmanial immunity. Mechanistically, our data indicate that GBPs facilitate the delivery of<jats:italic>Leishmania<\/jats:italic>into antimicrobial autolysosomes, thereby enhancing parasite clearance in nonphagocytic cells. We propose that this GBP-dependent host defense program makes nonphagocytic cells an inhospitable host cell type for<jats:italic>Leishmania<\/jats:italic>growth.<\/jats:p>","DOI":"10.1128\/mbio.01464-20","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T12:36:40Z","timestamp":1595853400000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Guanylate Binding Proteins Restrict Leishmania donovani Growth in Nonphagocytic Cells Independent of Parasitophorous Vacuolar Targeting"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0599-2286","authenticated-orcid":false,"given":"Arun Kumar","family":"Haldar","sequence":"first","affiliation":[{"name":"Division of Biochemistry, Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utsav","family":"Nigam","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rn","family":"Coers","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA"},{"name":"Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neena","family":"Goyal","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12546"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3118"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2016.04.032"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.4MR0516-223R"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2010.0102"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2010.07586.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2006.26.328"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3440"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1089\/10799900050198435"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2007.0086"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014246"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.11479"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/35000617"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)78125-3"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)36334-2"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2005.25.435"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04510"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1313"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-386931-9.00015-5"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.9614"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-004-0489-2"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-189886"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.06.005"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.02.019"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3210"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2017.10.013"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20182031"},{"key":"e_1_3_2_29_2","first-page":"1","volume-title":"The leishmaniases in biology and medicine","author":"Lainson R","year":"1987","unstructured":"Lainson R, Shaw JJ. 1987. 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