Show simple item record

dc.contributor.authorSchamber-Reis, Bruno Luiz Fonseca
dc.contributor.authorPetritus, Patricia M.
dc.contributor.authorCaetano, Braulia C.
dc.contributor.authorMartinez, Espiridion R.
dc.contributor.authorOkuda, Kendi
dc.contributor.authorGolenbock, Douglas T.
dc.contributor.authorScott, Phillip
dc.contributor.authorGazzinelli, Ricardo T
dc.date2022-08-11T08:08:22.000
dc.date.accessioned2022-08-23T15:52:45Z
dc.date.available2022-08-23T15:52:45Z
dc.date.issued2013-03-08
dc.date.submitted2013-07-08
dc.identifier.citationJ Biol Chem. 2013 Mar 8;288(10):7127-36. doi: 10.1074/jbc.M112.407684. <a href="http://dx.doi.org/10.1074/jbc.M112.407684">Link to article on publisher's site</a>
dc.identifier.issn0021-9258 (Linking)
dc.identifier.doi10.1074/jbc.M112.407684
dc.identifier.pmid23325805
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29210
dc.description.abstractThe mammalian homolog B1 of Unc-93 Caenorhabditis elegans known as UNC93B1 is a chaperone protein that mediates translocation of the nucleic acid-sensing Toll-like receptors (TLRs) from the endoplasmic reticulum to the endolysosomes. The triple deficient (UNC93B1 mutant) mice have a functional single point mutation in the UNC93B1 that results in non-functional TLR3, TLR7, and TLR9. Herein, we demonstrate that UNC93B1 mutant mice, in the C57BL/6 (resistant) genetic background, are highly susceptible to Leishmania major infection. Enhanced swelling of the footpad was associated with high levels of interleukin 10, decreased levels of interferon gamma, and increased parasitism. None of the single TLR3, TLR7, and TLR9 knock-out (KO) mice resemble the UNC93B1 mutant phenotype upon infection with L. major. Whereas the double TLR7/TLR9 KO showed a partial phenotype, the triple TLR3/TLR7/TLR9 KO mice were as susceptible as the UNC93B1 mutant mice, when infected with Leishmania parasites. Finally, we demonstrate that treatment with either anti-interleukin 10 receptor monoclonal antibody or recombinant interleukin 12 restored a robust anti-parasite TH1 response and reverted the susceptible phenotype of UNC93B1 mutant mice. Altogether, our results indicate the redundant and essential role of nucleic acid-sensing TLR3, TLR7 and TLR9 in inducing interleukin 12, development of a TH1 response, and resistance to L. major infection in resistant C57BL/6 mice.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23325805&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1074/jbc.M112.407684
dc.subjectAnimals
dc.subjectAntigens, CD4
dc.subjectCells, Cultured
dc.subjectDisease Resistance
dc.subjectFemale
dc.subjectHost-Parasite Interactions
dc.subjectInterferon-gamma
dc.subjectInterleukin-10
dc.subjectLeishmania major
dc.subjectLeishmaniasis, Cutaneous
dc.subjectMembrane Transport Proteins
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMice, Knockout
dc.subjectMutation
dc.subjectNucleic Acids
dc.subjectTh1 Cells
dc.subjectTime Factors
dc.subjectToll-Like Receptor 3
dc.subjectToll-Like Receptor 7
dc.subjectToll-Like Receptor 9
dc.subjectToll-Like Receptors
dc.subjectCytokines
dc.subjectInterferon
dc.subjectInnate Immunity
dc.subjectLeishmania
dc.subjectMyD88
dc.subjectToll-like Receptors (TLR)
dc.subjectUNC93B1
dc.subjectImmunology of Infectious Disease
dc.titleUNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume288
dc.source.issue10
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/144
dc.identifier.contextkey4295164
html.description.abstract<p>The mammalian homolog B1 of Unc-93 Caenorhabditis elegans known as UNC93B1 is a chaperone protein that mediates translocation of the nucleic acid-sensing Toll-like receptors (TLRs) from the endoplasmic reticulum to the endolysosomes. The triple deficient (UNC93B1 mutant) mice have a functional single point mutation in the UNC93B1 that results in non-functional TLR3, TLR7, and TLR9. Herein, we demonstrate that UNC93B1 mutant mice, in the C57BL/6 (resistant) genetic background, are highly susceptible to Leishmania major infection. Enhanced swelling of the footpad was associated with high levels of interleukin 10, decreased levels of interferon gamma, and increased parasitism. None of the single TLR3, TLR7, and TLR9 knock-out (KO) mice resemble the UNC93B1 mutant phenotype upon infection with L. major. Whereas the double TLR7/TLR9 KO showed a partial phenotype, the triple TLR3/TLR7/TLR9 KO mice were as susceptible as the UNC93B1 mutant mice, when infected with Leishmania parasites. Finally, we demonstrate that treatment with either anti-interleukin 10 receptor monoclonal antibody or recombinant interleukin 12 restored a robust anti-parasite TH1 response and reverted the susceptible phenotype of UNC93B1 mutant mice. Altogether, our results indicate the redundant and essential role of nucleic acid-sensing TLR3, TLR7 and TLR9 in inducing interleukin 12, development of a TH1 response, and resistance to L. major infection in resistant C57BL/6 mice.</p>
dc.identifier.submissionpathfaculty_pubs/144
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pages7127-36


This item appears in the following Collection(s)

Show simple item record