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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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/22/2597 |
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| author | Aditya Kumar Sharma Nahed Ismail |
| author_facet | Aditya Kumar Sharma Nahed Ismail |
| author_sort | Aditya Kumar Sharma |
| collection | DOAJ |
| 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. <i>Ehrlichia</i> 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 <i>Ehrlichia</i> 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. |
| first_indexed | 2024-03-09T16:56:28Z |
| format | Article |
| id | doaj.art-3250b972be604b88b816f4e0a48164aa |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T16:56:28Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-3250b972be604b88b816f4e0a48164aa2023-11-24T14:35:12ZengMDPI AGCells2073-44092023-11-011222259710.3390/cells12222597Non-Canonical Inflammasome Pathway: The Role of Cell Death and Inflammation in EhrlichiosisAditya Kumar Sharma0Nahed Ismail1Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USADepartment of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USAActivating 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. <i>Ehrlichia</i> 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 <i>Ehrlichia</i> 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.https://www.mdpi.com/2073-4409/12/22/2597<i>Ehrlichia</i> spp.non-canonical inflammasomePAMPsinflammasomeDAMPs |
| spellingShingle | Aditya Kumar Sharma Nahed Ismail Non-Canonical Inflammasome Pathway: The Role of Cell Death and Inflammation in Ehrlichiosis Cells <i>Ehrlichia</i> spp. non-canonical inflammasome PAMPs inflammasome DAMPs |
| 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 | <i>Ehrlichia</i> spp. non-canonical inflammasome PAMPs inflammasome DAMPs |
| url | https://www.mdpi.com/2073-4409/12/22/2597 |
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