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dc.contributor.authorStrijbis, Karin
dc.contributor.authorTafesse, Fikadu G.
dc.contributor.authorFairn, Gregory D.
dc.contributor.authorWitte, Martin D.
dc.contributor.authorDougan, Stephanie K.
dc.contributor.authorWatson, Nicki
dc.contributor.authorSpooner, Eric
dc.contributor.authorEsteban, Alexandre
dc.contributor.authorVyas, Valmik K.
dc.contributor.authorGrinstein, Sergio
dc.contributor.authorFink, Gerald R
dc.contributor.authorPloegh, Hidde
dc.date.accessioned2018-06-05T18:25:22Z
dc.date.available2018-06-05T18:25:22Z
dc.date.issued2013-06
dc.date.submitted2013-01
dc.identifier.issn1553-7374
dc.identifier.issn1553-7366
dc.identifier.urihttp://hdl.handle.net/1721.1/116115
dc.description.abstractPhagocytosis of the opportunistic fungal pathogen Candida albicans by cells of the innate immune system is vital to prevent infection. Dectin-1 is the major phagocytic receptor involved in anti-fungal immunity. We identify two new interacting proteins of Dectin-1 in macrophages, Bruton's Tyrosine Kinase (BTK) and Vav1. BTK and Vav1 are recruited to phagocytic cups containing C. albicans yeasts or hyphae but are absent from mature phagosomes. BTK and Vav1 localize to cuff regions surrounding the hyphae, while Dectin-1 lines the full length of the phagosome. BTK and Vav1 colocalize with the lipid PI(3,4,5)P3 and F-actin at the phagocytic cup, but not with diacylglycerol (DAG) which marks more mature phagosomal membranes. Using a selective BTK inhibitor, we show that BTK contributes to DAG synthesis at the phagocytic cup and the subsequent recruitment of PKCε. BTK- or Vav1-deficient peritoneal macrophages display a defect in both zymosan and C. albicans phagocytosis. Bone marrow-derived macrophages that lack BTK or Vav1 show reduced uptake of C. albicans, comparable to Dectin1-deficient cells. BTK- or Vav1-deficient mice are more susceptible to systemic C. albicans infection than wild type mice. This work identifies an important role for BTK and Vav1 in immune responses against C. albicans.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant GM040266)en_US
dc.publisherPublic Library of Science (PLoS)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1371/JOURNAL.PPAT.1003446en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.sourcePLoSen_US
dc.titleBruton's Tyrosine Kinase (BTK) and Vav1 Contribute to Dectin1-Dependent Phagocytosis of Candida albicans in Macrophagesen_US
dc.typeArticleen_US
dc.identifier.citationStrijbis, Karin et al. “Bruton’s Tyrosine Kinase (BTK) and Vav1 Contribute to Dectin1-Dependent Phagocytosis of Candida Albicans in Macrophages.” Edited by Robin Charles May. PLoS Pathogens 9, 6 (June 2013): e1003446 © 2013 Strijbis et alen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorFink, Gerald R
dc.contributor.mitauthorPloegh, Hidde
dc.relation.journalPLoS Pathogensen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2018-06-01T18:24:13Z
dspace.orderedauthorsStrijbis, Karin; Tafesse, Fikadu G.; Fairn, Gregory D.; Witte, Martin D.; Dougan, Stephanie K.; Watson, Nicki; Spooner, Eric; Esteban, Alexandre; Vyas, Valmik K.; Fink, Gerald R.; Grinstein, Sergio; Ploegh, Hidde L.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0003-3704-2899
dc.identifier.orcidhttps://orcid.org/0000-0002-1090-6071
mit.licensePUBLISHER_CCen_US


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