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Leishmania Lipophosphoglycan Triggers Caspase-11 and the Non-canonical Activation of the NLRP3 Inflammasome

Activation of the NLRP3 inflammasome by Leishmania parasites is critical for the outcome of leishmaniasis, a disease that affects millions of people worldwide. We investigate the mechanisms involved in NLRP3 activation and demonstrate that caspase-11 (CASP11) is activated in response to infection by...

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Autores principales: de Carvalho, Renan V.H., Andrade, Warrison A., Lima-Junior, Djalma S., Dilucca, Marisa, de Oliveira, Caroline V., Wang, Kun, Nogueira, Paula M., Rugani, Jeronimo N., Soares, Rodrigo P., Beverley, Stephen M., Shao, Feng, Zamboni, Dario S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022207/
https://www.ncbi.nlm.nih.gov/pubmed/30625325
http://dx.doi.org/10.1016/j.celrep.2018.12.047
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author de Carvalho, Renan V.H.
Andrade, Warrison A.
Lima-Junior, Djalma S.
Dilucca, Marisa
de Oliveira, Caroline V.
Wang, Kun
Nogueira, Paula M.
Rugani, Jeronimo N.
Soares, Rodrigo P.
Beverley, Stephen M.
Shao, Feng
Zamboni, Dario S.
author_facet de Carvalho, Renan V.H.
Andrade, Warrison A.
Lima-Junior, Djalma S.
Dilucca, Marisa
de Oliveira, Caroline V.
Wang, Kun
Nogueira, Paula M.
Rugani, Jeronimo N.
Soares, Rodrigo P.
Beverley, Stephen M.
Shao, Feng
Zamboni, Dario S.
author_sort de Carvalho, Renan V.H.
collection PubMed
description Activation of the NLRP3 inflammasome by Leishmania parasites is critical for the outcome of leishmaniasis, a disease that affects millions of people worldwide. We investigate the mechanisms involved in NLRP3 activation and demonstrate that caspase-11 (CASP11) is activated in response to infection by Leishmania species and triggers the non-canonical activation of NLRP3. This process accounts for host resistance to infection in macrophages and in vivo. We identify the parasite membrane glycoconjugate lipophosphoglycan (LPG) as the molecule involved in CASP11 activation. Cytosolic delivery of LPG in macrophages triggers CASP11 activation, and infections performed with Lpg1(−/−) parasites reduce CASP11/NLRP3 activation. Unlike bacterial LPS, purified LPG does not activate mouse CASP11 (or human Casp4) in vitro, suggesting the participation of additional molecules for LPG-mediated CASP11 activation. Our data identify a parasite molecule involved in CASP11 activation, thereby establishing the mechanisms underlying inflammasome activation in response to Leishmania species.
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spelling pubmed-80222072021-04-06 Leishmania Lipophosphoglycan Triggers Caspase-11 and the Non-canonical Activation of the NLRP3 Inflammasome de Carvalho, Renan V.H. Andrade, Warrison A. Lima-Junior, Djalma S. Dilucca, Marisa de Oliveira, Caroline V. Wang, Kun Nogueira, Paula M. Rugani, Jeronimo N. Soares, Rodrigo P. Beverley, Stephen M. Shao, Feng Zamboni, Dario S. Cell Rep Article Activation of the NLRP3 inflammasome by Leishmania parasites is critical for the outcome of leishmaniasis, a disease that affects millions of people worldwide. We investigate the mechanisms involved in NLRP3 activation and demonstrate that caspase-11 (CASP11) is activated in response to infection by Leishmania species and triggers the non-canonical activation of NLRP3. This process accounts for host resistance to infection in macrophages and in vivo. We identify the parasite membrane glycoconjugate lipophosphoglycan (LPG) as the molecule involved in CASP11 activation. Cytosolic delivery of LPG in macrophages triggers CASP11 activation, and infections performed with Lpg1(−/−) parasites reduce CASP11/NLRP3 activation. Unlike bacterial LPS, purified LPG does not activate mouse CASP11 (or human Casp4) in vitro, suggesting the participation of additional molecules for LPG-mediated CASP11 activation. Our data identify a parasite molecule involved in CASP11 activation, thereby establishing the mechanisms underlying inflammasome activation in response to Leishmania species. 2019-01-08 /pmc/articles/PMC8022207/ /pubmed/30625325 http://dx.doi.org/10.1016/j.celrep.2018.12.047 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
de Carvalho, Renan V.H.
Andrade, Warrison A.
Lima-Junior, Djalma S.
Dilucca, Marisa
de Oliveira, Caroline V.
Wang, Kun
Nogueira, Paula M.
Rugani, Jeronimo N.
Soares, Rodrigo P.
Beverley, Stephen M.
Shao, Feng
Zamboni, Dario S.
Leishmania Lipophosphoglycan Triggers Caspase-11 and the Non-canonical Activation of the NLRP3 Inflammasome
title Leishmania Lipophosphoglycan Triggers Caspase-11 and the Non-canonical Activation of the NLRP3 Inflammasome
title_full Leishmania Lipophosphoglycan Triggers Caspase-11 and the Non-canonical Activation of the NLRP3 Inflammasome
title_fullStr Leishmania Lipophosphoglycan Triggers Caspase-11 and the Non-canonical Activation of the NLRP3 Inflammasome
title_full_unstemmed Leishmania Lipophosphoglycan Triggers Caspase-11 and the Non-canonical Activation of the NLRP3 Inflammasome
title_short Leishmania Lipophosphoglycan Triggers Caspase-11 and the Non-canonical Activation of the NLRP3 Inflammasome
title_sort leishmania lipophosphoglycan triggers caspase-11 and the non-canonical activation of the nlrp3 inflammasome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022207/
https://www.ncbi.nlm.nih.gov/pubmed/30625325
http://dx.doi.org/10.1016/j.celrep.2018.12.047
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