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Non-Canonical Inflammasome Pathway: The Role of Cell Death and Inflammation in Ehrlichiosis

Activating inflammatory caspases and releasing pro-inflammatory mediators are two essential functions of inflammasomes which are triggered in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). The canonical inflammasome pathway involves the ac...

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Autores principales: Sharma, Aditya Kumar, Ismail, Nahed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10670716/
https://www.ncbi.nlm.nih.gov/pubmed/37998332
http://dx.doi.org/10.3390/cells12222597
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author Sharma, Aditya Kumar
Ismail, Nahed
author_facet Sharma, Aditya Kumar
Ismail, Nahed
author_sort Sharma, Aditya Kumar
collection PubMed
description Activating inflammatory caspases and releasing pro-inflammatory mediators are two essential functions of inflammasomes which are triggered in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). The canonical inflammasome pathway involves the activation of inflammasome and its downstream pathway via the adaptor ASC protein, which causes caspase 1 activation and, eventually, the cleavage of pro-IL-1b and pro-IL-18. The non-canonical inflammasome pathway is induced upon detecting cytosolic lipopolysaccharide (LPS) by NLRP3 inflammasome in Gram-negative bacteria. The activation of NLRP3 triggers the cleavage of murine caspase 11 (human caspase 4 or caspase 5), which results in the formation of pores (via gasdermin) to cause pyroptosis. Ehrlichia is an obligately intracellular bacterium which is responsible for causing human monocytic ehrlichiosis (HME), a potentially lethal disease similar to toxic shock syndrome and septic shock syndrome. Several studies have indicated that canonical and non-canonical inflammasome activation is a crucial pathogenic mechanism that induces dysregulated inflammation and host cellular death in the pathophysiology of HME. Mechanistically, the activation of canonical and non-canonical inflammasome pathways affected by virulent Ehrlichia infection is due to a block in autophagy. This review aims to explore the significance of non-canonical inflammasomes in ehrlichiosis, and how the pathways involving caspases (with the exception of caspase 1) contribute to the pathophysiology of severe and fatal ehrlichiosis. Improving our understanding of the non-canonical inflammatory pathway that cause cell death and inflammation in ehrlichiosis will help the advancement of innovative therapeutic, preventative, and diagnostic approaches to the treatment of ehrlichiosis.
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spelling pubmed-106707162023-11-09 Non-Canonical Inflammasome Pathway: The Role of Cell Death and Inflammation in Ehrlichiosis Sharma, Aditya Kumar Ismail, Nahed Cells Review Activating inflammatory caspases and releasing pro-inflammatory mediators are two essential functions of inflammasomes which are triggered in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). The canonical inflammasome pathway involves the activation of inflammasome and its downstream pathway via the adaptor ASC protein, which causes caspase 1 activation and, eventually, the cleavage of pro-IL-1b and pro-IL-18. The non-canonical inflammasome pathway is induced upon detecting cytosolic lipopolysaccharide (LPS) by NLRP3 inflammasome in Gram-negative bacteria. The activation of NLRP3 triggers the cleavage of murine caspase 11 (human caspase 4 or caspase 5), which results in the formation of pores (via gasdermin) to cause pyroptosis. Ehrlichia is an obligately intracellular bacterium which is responsible for causing human monocytic ehrlichiosis (HME), a potentially lethal disease similar to toxic shock syndrome and septic shock syndrome. Several studies have indicated that canonical and non-canonical inflammasome activation is a crucial pathogenic mechanism that induces dysregulated inflammation and host cellular death in the pathophysiology of HME. Mechanistically, the activation of canonical and non-canonical inflammasome pathways affected by virulent Ehrlichia infection is due to a block in autophagy. This review aims to explore the significance of non-canonical inflammasomes in ehrlichiosis, and how the pathways involving caspases (with the exception of caspase 1) contribute to the pathophysiology of severe and fatal ehrlichiosis. Improving our understanding of the non-canonical inflammatory pathway that cause cell death and inflammation in ehrlichiosis will help the advancement of innovative therapeutic, preventative, and diagnostic approaches to the treatment of ehrlichiosis. MDPI 2023-11-09 /pmc/articles/PMC10670716/ /pubmed/37998332 http://dx.doi.org/10.3390/cells12222597 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Sharma, Aditya Kumar
Ismail, Nahed
Non-Canonical Inflammasome Pathway: The Role of Cell Death and Inflammation in Ehrlichiosis
title Non-Canonical Inflammasome Pathway: The Role of Cell Death and Inflammation in Ehrlichiosis
title_full Non-Canonical Inflammasome Pathway: The Role of Cell Death and Inflammation in Ehrlichiosis
title_fullStr Non-Canonical Inflammasome Pathway: The Role of Cell Death and Inflammation in Ehrlichiosis
title_full_unstemmed Non-Canonical Inflammasome Pathway: The Role of Cell Death and Inflammation in Ehrlichiosis
title_short Non-Canonical Inflammasome Pathway: The Role of Cell Death and Inflammation in Ehrlichiosis
title_sort non-canonical inflammasome pathway: the role of cell death and inflammation in ehrlichiosis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10670716/
https://www.ncbi.nlm.nih.gov/pubmed/37998332
http://dx.doi.org/10.3390/cells12222597
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