{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:16:19Z","timestamp":1790381779152,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010237","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000}}],"reference-count":103,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["Graduate Research Fellowship"],"award-info":[{"award-number":["Graduate Research Fellowship"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI136735"],"award-info":[{"award-number":["R01AI136735"]}],"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":["2R37AI066224"],"award-info":[{"award-number":["2R37AI066224"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["1DP2HD084069-01"],"award-info":[{"award-number":["1DP2HD084069-01"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The fungal pathogen\n                    <jats:italic>Histoplasma capsulatum<\/jats:italic>\n                    (\n                    <jats:italic>Hc<\/jats:italic>\n                    ) invades, replicates within, and destroys macrophages. To interrogate the molecular mechanisms underlying this interaction, we conducted a host-directed CRISPR-Cas9 screen and identified 361 genes that modify macrophage susceptibility to\n                    <jats:italic>Hc<\/jats:italic>\n                    infection, greatly expanding our understanding of host gene networks targeted by\n                    <jats:italic>Hc<\/jats:italic>\n                    . We identified pathways that have not been previously implicated in\n                    <jats:italic>Hc<\/jats:italic>\n                    interaction with macrophages, including the ragulator complex (involved in nutrient stress sensing), glycosylation enzymes, protein degradation machinery, mitochondrial respiration genes, solute transporters, and the ER membrane complex (EMC). The highest scoring protective hits included the complement C3a receptor (C3aR), a G-protein coupled receptor (GPCR) that recognizes the complement fragment C3a. Although it is known that complement components react with the fungal surface, leading to opsonization and release of small peptide fragments such as C3a, a role for C3aR in macrophage interactions with fungi has not been elucidated. We demonstrated that whereas C3aR is dispensable for macrophage phagocytosis of bacteria and latex beads, it is critical for optimal macrophage capture of pathogenic fungi, including\n                    <jats:italic>Hc<\/jats:italic>\n                    , the ubiquitous fungal pathogen\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    , and the causative agent of Valley Fever\n                    <jats:italic>Coccidioides posadasii<\/jats:italic>\n                    . We showed that C3aR localizes to the early phagosome during\n                    <jats:italic>Hc<\/jats:italic>\n                    infection where it coordinates the formation of actin-rich membrane protrusions that promote\n                    <jats:italic>Hc<\/jats:italic>\n                    capture. We also showed that the EMC promotes surface expression of C3aR, likely explaining its identification in our screen. Taken together, our results provide new insight into host processes that affect\n                    <jats:italic>Hc<\/jats:italic>\n                    -macrophage interactions and uncover a novel and specific role for C3aR in macrophage recognition of fungi.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010237","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T15:33:03Z","timestamp":1664465583000},"page":"e1010237","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Genome-scale CRISPR screening reveals that C3aR signaling is critical for rapid capture of fungi by macrophages"],"prefix":"10.1371","volume":"18","author":[{"given":"Allison","family":"Cohen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin E.","family":"Jeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Voorhies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Symington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nebat","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa A.","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Bassik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3987-7534","authenticated-orcid":true,"given":"Anita","family":"Sil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,9,29]]},"reference":[{"issue":"1","key":"ppat.1010237.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/10408410903241444","article-title":"Epidemiology of invasive mycoses in North America","volume":"36","author":"MA Pfaller","year":"2010","journal-title":"Critical reviews in microbiology"},{"issue":"3","key":"ppat.1010237.ref002","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1189\/jlb.0308154","article-title":"Histoplasma capsulatum manifests preferential invasion of phagocytic subpopulations in murine lungs","volume":"84","author":"GS Deepe","year":"2008","journal-title":"J Leukoc 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Immunol"},{"issue":"2","key":"ppat.1010237.ref027","doi-asserted-by":"crossref","first-page":"688","DOI":"10.4049\/jimmunol.1700318","article-title":"Monitoring C3aR Expression Using a Floxed tdTomato-C3aR Reporter Knock-in Mouse","volume":"199","author":"KM Quell","year":"2017","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"issue":"5","key":"ppat.1010237.ref028","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1002\/(SICI)1521-4141(199805)28:05<1570::AID-IMMU1570>3.0.CO;2-6","article-title":"Anaphylatoxin C3a but not C3a(desArg) is a chemotaxin for the mouse macrophage cell line J774","volume":"28","author":"J Zwirner","year":"1998","journal-title":"European journal of immunology"},{"issue":"8","key":"ppat.1010237.ref029","doi-asserted-by":"crossref","first-page":"3542","DOI":"10.4049\/jimmunol.1403068","article-title":"Is the complement activation product C3a a proinflammatory molecule? 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I. 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Conventional Dendritic Cells Are Critical for TLR7\/9-Dependent Host Defense against Histoplasma capsulatum, an Endemic Fungal Pathogen of Humans","volume":"12","author":"N Van Prooyen","year":"2016","journal-title":"PLoS pathogens"},{"issue":"3","key":"ppat.1010237.ref093","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1080\/02681218880000211","article-title":"Quantitative plating of Histoplasma capsulatum without addition of conditioned medium or siderophores","volume":"26","author":"PL Worsham","year":"1988","journal-title":"Journal of medical and veterinary mycology: bi-monthly publication of the International Society for Human and Animal Mycology"},{"issue":"1","key":"ppat.1010237.ref094","doi-asserted-by":"crossref","first-page":"e113","DOI":"10.1002\/cpmc.113","article-title":"Proper Care and Feeding of Coccidioides: A Laboratorian\u2019s Guide to Cultivating the Dimorphic Stages of C. immitis and C. posadasii","volume":"58","author":"HL 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