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dc.contributor.authorMelo, Mariane B.
dc.contributor.authorKasperkovitz, Pia
dc.contributor.authorCerny, Anna M.
dc.contributor.authorKonen-Waisman, Stephanie
dc.contributor.authorKurt-Jones, Evelyn A.
dc.contributor.authorLien, Egil
dc.contributor.authorBeutler, Bruce
dc.contributor.authorHoward, Jonathan C.
dc.contributor.authorGolenbock, Douglas T.
dc.contributor.authorGazzinelli, Ricardo T.
dc.date2022-08-11T08:09:10.000
dc.date.accessioned2022-08-23T16:19:55Z
dc.date.available2022-08-23T16:19:55Z
dc.date.issued2010-08-01
dc.date.submitted2018-03-20
dc.identifier.citation<p>PLoS Pathog. 2010 Aug 26;6(8):e1001071. doi: 10.1371/journal.ppat.1001071. <a href="https://doi.org/10.1371/journal.ppat.1001071">Link to article on publisher's site</a></p>
dc.identifier.issn1553-7366 (Linking)
dc.identifier.doi10.1371/journal.ppat.1001071
dc.identifier.pmid20865117
dc.identifier.urihttp://hdl.handle.net/20.500.14038/35166
dc.description.abstractUNC93B1 associates with Toll-Like Receptor (TLR) 3, TLR7 and TLR9, mediating their translocation from the endoplasmic reticulum to the endolysosome, hence allowing proper activation by nucleic acid ligands. We found that the triple deficient '3d' mice, which lack functional UNC93B1, are hyper-susceptible to infection with Toxoplasma gondii. We established that while mounting a normal systemic pro-inflammatory response, i.e. producing abundant MCP-1, IL-6, TNFalpha and IFNgamma, the 3d mice were unable to control parasite replication. Nevertheless, infection of reciprocal bone marrow chimeras between wild-type and 3d mice with T. gondii demonstrated a primary role of hemopoietic cell lineages in the enhanced susceptibility of UNC93B1 mutant mice. The protective role mediated by UNC93B1 to T. gondii infection was associated with impaired IL-12 responses and delayed IFNgamma by spleen cells. Notably, in macrophages infected with T. gondii, UNC93B1 accumulates on the parasitophorous vacuole. Furthermore, upon in vitro infection the rate of tachyzoite replication was enhanced in non-activated macrophages carrying mutant UNC93B1 as compared to wild type gene. Strikingly, the role of UNC93B1 on intracellular parasite growth appears to be independent of TLR function. Altogether, our results reveal a critical role for UNC93B1 on induction of IL-12/IFNgamma production as well as autonomous control of Toxoplasma replication by macrophages.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=20865117&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectImmunity
dc.subjectImmunology and Infectious Disease
dc.subjectImmunology of Infectious Disease
dc.subjectInfectious Disease
dc.subjectVirology
dc.titleUNC93B1 mediates host resistance to infection with Toxoplasma gondii
dc.typeJournal Article
dc.source.journaltitlePLoS pathogens
dc.source.volume6
dc.source.issue8
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1387&amp;context=infdis_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/infdis_pp/386
dc.identifier.contextkey11814592
refterms.dateFOA2022-08-23T16:19:56Z
html.description.abstract<p>UNC93B1 associates with Toll-Like Receptor (TLR) 3, TLR7 and TLR9, mediating their translocation from the endoplasmic reticulum to the endolysosome, hence allowing proper activation by nucleic acid ligands. We found that the triple deficient '3d' mice, which lack functional UNC93B1, are hyper-susceptible to infection with Toxoplasma gondii. We established that while mounting a normal systemic pro-inflammatory response, i.e. producing abundant MCP-1, IL-6, TNFalpha and IFNgamma, the 3d mice were unable to control parasite replication. Nevertheless, infection of reciprocal bone marrow chimeras between wild-type and 3d mice with T. gondii demonstrated a primary role of hemopoietic cell lineages in the enhanced susceptibility of UNC93B1 mutant mice. The protective role mediated by UNC93B1 to T. gondii infection was associated with impaired IL-12 responses and delayed IFNgamma by spleen cells. Notably, in macrophages infected with T. gondii, UNC93B1 accumulates on the parasitophorous vacuole. Furthermore, upon in vitro infection the rate of tachyzoite replication was enhanced in non-activated macrophages carrying mutant UNC93B1 as compared to wild type gene. Strikingly, the role of UNC93B1 on intracellular parasite growth appears to be independent of TLR function. Altogether, our results reveal a critical role for UNC93B1 on induction of IL-12/IFNgamma production as well as autonomous control of Toxoplasma replication by macrophages.</p>
dc.identifier.submissionpathinfdis_pp/386
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pagese1001071


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