UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2013 |
| Outros Autores: | , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/30199 |
Resumo: | 2020-01-01 |
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Schamber-Reis, Bruno Luiz FonsecaPetritus, Patricia M.Caetano, Braulia C.Martinez, Espiridion R.Okuda, KendiGolenbock, Douglas TaylorScott, PhillipGazzinelli, Ricardo Tostes2018-11-26T16:56:37Z2018-11-26T16:56:37Z2013SCHAMBER-REIS, Bruno Luiz Fonseca et al. UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major. J Biol Chem.; v. 288, n. 10, p. 7127-7136.0021-9258https://www.arca.fiocruz.br/handle/icict/3019910.1074/jbc.M112.407684engAmerican Society for Biochemistry and Molecular BiologyCitocinas / InterferonImunidade inataLeishmaniaMyD88Receptores Toll-like (TLR)UNC93B1Cytokines/InterferonInnate ImmunityLeishmaniaMyD88Toll-like Receptors (TLR)UNC93B1UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania majorinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2020-01-01University of Massachusetts Medical School. Worcester, MA, USASchool of Veterinary Medicine.University of Pennsylvania. Philadelphia, PE, USAUniversity of Massachusetts Medical School. Worcester, MA, USAUniversity of Massachusetts Medical School. Worcester, MA, USAUniversity of Massachusetts Medical School. Worcester, MA, USAUniversity of Massachusetts Medical School. Worcester, MA, USA/ Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilSchool of Veterinary Medicine.University of Pennsylvania. Philadelphia, PE, USAUniversity of Massachusetts Medical School. Worcester, MA, USA/ Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/ Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, BrazilThe 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 γ, 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.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/30199/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALUNC93B1 and Nucleic Acid-sensing .pdfUNC93B1 and Nucleic Acid-sensing .pdfapplication/pdf7086951https://www.arca.fiocruz.br/bitstream/icict/30199/2/UNC93B1%20and%20Nucleic%20Acid-sensing%20.pdfda30d5d98a56f36cccd60cfa86547835MD52TEXTUNC93B1 and Nucleic Acid-sensing .pdf.txtUNC93B1 and Nucleic Acid-sensing .pdf.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major |
| title |
UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major |
| spellingShingle |
UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major Schamber-Reis, Bruno Luiz Fonseca Citocinas / Interferon Imunidade inata Leishmania MyD88 Receptores Toll-like (TLR) UNC93B1 Cytokines/Interferon Innate Immunity Leishmania MyD88 Toll-like Receptors (TLR) UNC93B1 |
| title_short |
UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major |
| title_full |
UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major |
| title_fullStr |
UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major |
| title_full_unstemmed |
UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major |
| title_sort |
UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major |
| author |
Schamber-Reis, Bruno Luiz Fonseca |
| author_facet |
Schamber-Reis, Bruno Luiz Fonseca Petritus, Patricia M. Caetano, Braulia C. Martinez, Espiridion R. Okuda, Kendi Golenbock, Douglas Taylor Scott, Phillip Gazzinelli, Ricardo Tostes |
| author_role |
author |
| author2 |
Petritus, Patricia M. Caetano, Braulia C. Martinez, Espiridion R. Okuda, Kendi Golenbock, Douglas Taylor Scott, Phillip Gazzinelli, Ricardo Tostes |
| author2_role |
author author author author author author author |
| dc.contributor.author.fl_str_mv |
Schamber-Reis, Bruno Luiz Fonseca Petritus, Patricia M. Caetano, Braulia C. Martinez, Espiridion R. Okuda, Kendi Golenbock, Douglas Taylor Scott, Phillip Gazzinelli, Ricardo Tostes |
| dc.subject.other.pt_BR.fl_str_mv |
Citocinas / Interferon Imunidade inata Leishmania MyD88 Receptores Toll-like (TLR) UNC93B1 |
| topic |
Citocinas / Interferon Imunidade inata Leishmania MyD88 Receptores Toll-like (TLR) UNC93B1 Cytokines/Interferon Innate Immunity Leishmania MyD88 Toll-like Receptors (TLR) UNC93B1 |
| dc.subject.en.pt_BR.fl_str_mv |
Cytokines/Interferon Innate Immunity Leishmania MyD88 Toll-like Receptors (TLR) UNC93B1 |
| description |
2020-01-01 |
| publishDate |
2013 |
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2013 |
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2018-11-26T16:56:37Z |
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2018-11-26T16:56:37Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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SCHAMBER-REIS, Bruno Luiz Fonseca et al. UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major. J Biol Chem.; v. 288, n. 10, p. 7127-7136. |
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https://www.arca.fiocruz.br/handle/icict/30199 |
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0021-9258 |
| dc.identifier.doi.none.fl_str_mv |
10.1074/jbc.M112.407684 |
| identifier_str_mv |
SCHAMBER-REIS, Bruno Luiz Fonseca et al. UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major. J Biol Chem.; v. 288, n. 10, p. 7127-7136. 0021-9258 10.1074/jbc.M112.407684 |
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American Society for Biochemistry and Molecular Biology |
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American Society for Biochemistry and Molecular Biology |
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