NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis.
Burkholderia pseudomallei causes the tropical infection melioidosis. Pneumonia is a common manifestation of melioidosis and is associated with high mortality. Understanding the key elements of host defense is essential to developing new therapeutics for melioidosis. As a flagellated bacterium encodi...
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ftdoajarticles:oai:doaj.org/article:20fed37201ba44828db72d9b63bc1dfa 2023-05-15T15:10:07+02:00 NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis. T Eoin West Nicolle D Myers Narisara Chantratita Wirongrong Chierakul Direk Limmathurotsakul Vanaporn Wuthiekanun Edward A Miao Adeline M Hajjar Sharon J Peacock H Denny Liggitt Shawn J Skerrett 2014-09-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003178 https://doaj.org/article/20fed37201ba44828db72d9b63bc1dfa EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4169243?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003178 https://doaj.org/article/20fed37201ba44828db72d9b63bc1dfa PLoS Neglected Tropical Diseases, Vol 8, Iss 9, p e3178 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003178 2022-12-31T14:05:48Z Burkholderia pseudomallei causes the tropical infection melioidosis. Pneumonia is a common manifestation of melioidosis and is associated with high mortality. Understanding the key elements of host defense is essential to developing new therapeutics for melioidosis. As a flagellated bacterium encoding type III secretion systems, B. pseudomallei may trigger numerous host pathogen recognition receptors. TLR5 is a flagellin sensor located on the plasma membrane. NLRC4, along with NAIP proteins, assembles a canonical caspase-1-dependent inflammasome in the cytoplasm that responds to flagellin (in mice) and type III secretion system components (in mice and humans). In a murine model of respiratory melioidosis, Tlr5 and Nlrc4 each contributed to survival. Mice deficient in both Tlr5 and Nlrc4 were not more susceptible than single knockout animals. Deficiency of Casp1/Casp11 resulted in impaired bacterial control in the lung and spleen; in the lung much of this effect was attributable to Nlrc4, despite relative preservation of pulmonary IL-1β production in Nlrc4(-/-) mice. Histologically, deficiency of Casp1/Casp11 imparted more severe pulmonary inflammation than deficiency of Nlrc4. The human NLRC4 region polymorphism rs6757121 was associated with survival in melioidosis patients with pulmonary involvement. Co-inheritance of rs6757121 and a functional TLR5 polymorphism had an additive effect on survival. Our results show that NLRC4 and TLR5, key components of two flagellin sensing pathways, each contribute to host defense in respiratory melioidosis. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 9 e3178 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 T Eoin West Nicolle D Myers Narisara Chantratita Wirongrong Chierakul Direk Limmathurotsakul Vanaporn Wuthiekanun Edward A Miao Adeline M Hajjar Sharon J Peacock H Denny Liggitt Shawn J Skerrett NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis. |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Burkholderia pseudomallei causes the tropical infection melioidosis. Pneumonia is a common manifestation of melioidosis and is associated with high mortality. Understanding the key elements of host defense is essential to developing new therapeutics for melioidosis. As a flagellated bacterium encoding type III secretion systems, B. pseudomallei may trigger numerous host pathogen recognition receptors. TLR5 is a flagellin sensor located on the plasma membrane. NLRC4, along with NAIP proteins, assembles a canonical caspase-1-dependent inflammasome in the cytoplasm that responds to flagellin (in mice) and type III secretion system components (in mice and humans). In a murine model of respiratory melioidosis, Tlr5 and Nlrc4 each contributed to survival. Mice deficient in both Tlr5 and Nlrc4 were not more susceptible than single knockout animals. Deficiency of Casp1/Casp11 resulted in impaired bacterial control in the lung and spleen; in the lung much of this effect was attributable to Nlrc4, despite relative preservation of pulmonary IL-1β production in Nlrc4(-/-) mice. Histologically, deficiency of Casp1/Casp11 imparted more severe pulmonary inflammation than deficiency of Nlrc4. The human NLRC4 region polymorphism rs6757121 was associated with survival in melioidosis patients with pulmonary involvement. Co-inheritance of rs6757121 and a functional TLR5 polymorphism had an additive effect on survival. Our results show that NLRC4 and TLR5, key components of two flagellin sensing pathways, each contribute to host defense in respiratory melioidosis. |
format |
Article in Journal/Newspaper |
author |
T Eoin West Nicolle D Myers Narisara Chantratita Wirongrong Chierakul Direk Limmathurotsakul Vanaporn Wuthiekanun Edward A Miao Adeline M Hajjar Sharon J Peacock H Denny Liggitt Shawn J Skerrett |
author_facet |
T Eoin West Nicolle D Myers Narisara Chantratita Wirongrong Chierakul Direk Limmathurotsakul Vanaporn Wuthiekanun Edward A Miao Adeline M Hajjar Sharon J Peacock H Denny Liggitt Shawn J Skerrett |
author_sort |
T Eoin West |
title |
NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis. |
title_short |
NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis. |
title_full |
NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis. |
title_fullStr |
NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis. |
title_full_unstemmed |
NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis. |
title_sort |
nlrc4 and tlr5 each contribute to host defense in respiratory melioidosis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0003178 https://doaj.org/article/20fed37201ba44828db72d9b63bc1dfa |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 9, p e3178 (2014) |
op_relation |
http://europepmc.org/articles/PMC4169243?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003178 https://doaj.org/article/20fed37201ba44828db72d9b63bc1dfa |
op_doi |
https://doi.org/10.1371/journal.pntd.0003178 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
8 |
container_issue |
9 |
container_start_page |
e3178 |
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