{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T12:17:47Z","timestamp":1792844267423,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010003","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000}}],"reference-count":103,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T00:00:00Z","timestamp":1652832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI148249"],"award-info":[{"award-number":["R01AI148249"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI148249"],"award-info":[{"award-number":["R01AI148249"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32AI007532"],"award-info":[{"award-number":["T32AI007532"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K99AI137442"],"award-info":[{"award-number":["K99AI137442"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32AI007532"],"award-info":[{"award-number":["T32AI007532"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32A1055400"],"award-info":[{"award-number":["T32A1055400"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    is a leading cause of severe diarrhea and diarrheal-related death in children worldwide. As an obligate intracellular parasite,\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    relies on intestinal epithelial cells to provide a niche for its growth and survival, but little is known about the contributions that the infected cell makes to this relationship. Here we conducted a genome wide CRISPR\/Cas9 knockout screen to discover host genes that influence\n                    <jats:italic>Cryptosporidium parvum<\/jats:italic>\n                    infection and\/or host cell survival. Gene enrichment analysis indicated that the host interferon response, glycosaminoglycan (GAG) and glycosylphosphatidylinositol (GPI) anchor biosynthesis are important determinants of susceptibility to\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>parvum<\/jats:italic>\n                    infection and impact on the viability of host cells in the context of parasite infection. Several of these pathways are linked to parasite attachment and invasion and C-type lectins on the surface of the parasite. Evaluation of transcript and protein induction of innate interferons revealed a pronounced type III interferon response to\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    in human cells as well as in mice. Treatment of mice with IFN\u03bb reduced infection burden and protected immunocompromised mice from severe outcomes including death, with effects that required STAT1 signaling in the enterocyte. Initiation of this type III interferon response was dependent on sustained intracellular growth and mediated by the pattern recognition receptor TLR3. We conclude that host cell intrinsic recognition of\n                    <jats:italic>Cryptosporidium<\/jats:italic>\n                    results in IFN\u03bb production critical to early protection against this infection.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010003","type":"journal-article","created":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T13:37:52Z","timestamp":1652881072000},"page":"e1010003","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":47,"title":["A genetic screen identifies a protective type III interferon response to Cryptosporidium that requires TLR3 dependent recognition"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1078-4841","authenticated-orcid":true,"given":"Alexis R.","family":"Gibson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Sateriale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Dumaine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie B.","family":"Engiles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan D.","family":"Pardy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1666-9983","authenticated-orcid":true,"given":"Jodi A.","family":"Gullicksrud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9278-0697","authenticated-orcid":true,"given":"Keenan M.","family":"O\u2019Dea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3707-9889","authenticated-orcid":true,"given":"John G.","family":"Doench","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2865-4589","authenticated-orcid":true,"given":"Daniel P.","family":"Beiting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7426-432X","authenticated-orcid":true,"given":"Boris","family":"Striepen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,5,18]]},"reference":[{"issue":"19","key":"ppat.1010003.ref001","doi-asserted-by":"crossref","first-page":"547","DOI":"10.15585\/mmwr.mm6719a3","article-title":"Outbreaks Associated with Treated Recreational Water\u2014United States, 2000\u20132014","volume":"67","author":"MC Hlavsa","year":"2018","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"9","key":"ppat.1010003.ref002","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1093\/oxfordjournals.aje.a009015","article-title":"Cryptosporidiosis among Patients Infected with Human Immunodeficiency Virus: Factors Related to Symptomatic Infection and Survival","volume":"144","author":"JM Colford","year":"1996","journal-title":"American Journal of Epidemiology"},{"issue":"9888","key":"ppat.1010003.ref003","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0140-6736(13)60844-2","article-title":"Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study","volume":"382","author":"KL Kotloff","year":"2013","journal-title":"The Lancet"},{"issue":"6","key":"ppat.1010003.ref004","doi-asserted-by":"crossref","first-page":"e1009445","DOI":"10.1371\/journal.ppat.1009445","article-title":"Nonsterile immunity to cryptosporidiosis in infants is associated with mucosal IgA against the sporozoite and protection from malnutrition","volume":"17","author":"M Kabir","year":"2021","journal-title":"PLOS Pathogens"},{"issue":"3","key":"ppat.1010003.ref005","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.4049\/jimmunol.147.3.1014","article-title":"Cryptosporidium infection in an adult mouse model. 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