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Autophagy proteins regulate innate immune response by inhibiting NALP3 inflammasome-mediated mitochondrial DNA release
Autophagy, a cellular process for organelle and protein turnover, regulates innate immune responses. We demonstrate that depletion of autophagic proteins microtubule associated protein-1 light chain 3B (LC3B) and Beclin 1 enhances caspase-1 activation and secretion of interleukin-1β and interleukin-...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079381/ https://www.ncbi.nlm.nih.gov/pubmed/21151103 http://dx.doi.org/10.1038/ni.1980 |
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author | Nakahira, Kiichi Haspel, Jeffrey Adam Rathinam, Vijay AK Lee, Seon-Jin Dolinay, Tamas Lam, Hilaire C Englert, Joshua A Rabinovitch, Marlene Cernadas, Manuela Kim, Hong Pyo Fitzgerald, Katherine A Ryter, Stefan W Choi, Augustine MK |
author_facet | Nakahira, Kiichi Haspel, Jeffrey Adam Rathinam, Vijay AK Lee, Seon-Jin Dolinay, Tamas Lam, Hilaire C Englert, Joshua A Rabinovitch, Marlene Cernadas, Manuela Kim, Hong Pyo Fitzgerald, Katherine A Ryter, Stefan W Choi, Augustine MK |
author_sort | Nakahira, Kiichi |
collection | PubMed |
description | Autophagy, a cellular process for organelle and protein turnover, regulates innate immune responses. We demonstrate that depletion of autophagic proteins microtubule associated protein-1 light chain 3B (LC3B) and Beclin 1 enhances caspase-1 activation and secretion of interleukin-1β and interleukin-18. Autophagic protein depletion promoted accumulation of dysfunctional mitochondria and cytosolic translocation of mitochondrial DNA (mtDNA) in response to lipopolysaccharide (LPS) and ATP in macrophages. Release of mtDNA into the cytosol depended on the NALP3 inflammasome and mitochondrial ROS. Cytosolic mtDNA contributed to IL-1β and IL-18 secretion in response to LPS and ATP. LC3B-deficient mice produced more caspase-1-dependent cytokines in two sepsis models and were susceptible to LPS-induced mortality. Our study suggests that autophagic proteins regulate NALP3-dependent inflammation by preserving mitochondrial integrity. |
format | Text |
id | pubmed-3079381 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
record_format | MEDLINE/PubMed |
spelling | pubmed-30793812011-09-01 Autophagy proteins regulate innate immune response by inhibiting NALP3 inflammasome-mediated mitochondrial DNA release Nakahira, Kiichi Haspel, Jeffrey Adam Rathinam, Vijay AK Lee, Seon-Jin Dolinay, Tamas Lam, Hilaire C Englert, Joshua A Rabinovitch, Marlene Cernadas, Manuela Kim, Hong Pyo Fitzgerald, Katherine A Ryter, Stefan W Choi, Augustine MK Nat Immunol Article Autophagy, a cellular process for organelle and protein turnover, regulates innate immune responses. We demonstrate that depletion of autophagic proteins microtubule associated protein-1 light chain 3B (LC3B) and Beclin 1 enhances caspase-1 activation and secretion of interleukin-1β and interleukin-18. Autophagic protein depletion promoted accumulation of dysfunctional mitochondria and cytosolic translocation of mitochondrial DNA (mtDNA) in response to lipopolysaccharide (LPS) and ATP in macrophages. Release of mtDNA into the cytosol depended on the NALP3 inflammasome and mitochondrial ROS. Cytosolic mtDNA contributed to IL-1β and IL-18 secretion in response to LPS and ATP. LC3B-deficient mice produced more caspase-1-dependent cytokines in two sepsis models and were susceptible to LPS-induced mortality. Our study suggests that autophagic proteins regulate NALP3-dependent inflammation by preserving mitochondrial integrity. 2010-12-12 2011-03 /pmc/articles/PMC3079381/ /pubmed/21151103 http://dx.doi.org/10.1038/ni.1980 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Nakahira, Kiichi Haspel, Jeffrey Adam Rathinam, Vijay AK Lee, Seon-Jin Dolinay, Tamas Lam, Hilaire C Englert, Joshua A Rabinovitch, Marlene Cernadas, Manuela Kim, Hong Pyo Fitzgerald, Katherine A Ryter, Stefan W Choi, Augustine MK Autophagy proteins regulate innate immune response by inhibiting NALP3 inflammasome-mediated mitochondrial DNA release |
title | Autophagy proteins regulate innate immune response by inhibiting NALP3 inflammasome-mediated mitochondrial DNA release |
title_full | Autophagy proteins regulate innate immune response by inhibiting NALP3 inflammasome-mediated mitochondrial DNA release |
title_fullStr | Autophagy proteins regulate innate immune response by inhibiting NALP3 inflammasome-mediated mitochondrial DNA release |
title_full_unstemmed | Autophagy proteins regulate innate immune response by inhibiting NALP3 inflammasome-mediated mitochondrial DNA release |
title_short | Autophagy proteins regulate innate immune response by inhibiting NALP3 inflammasome-mediated mitochondrial DNA release |
title_sort | autophagy proteins regulate innate immune response by inhibiting nalp3 inflammasome-mediated mitochondrial dna release |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079381/ https://www.ncbi.nlm.nih.gov/pubmed/21151103 http://dx.doi.org/10.1038/ni.1980 |
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