التفاصيل البيبلوغرافية
| العنوان: |
A Type VI Secretion System in Burkholderia Species cenocepacia and orbicola Triggers Distinct Macrophage Death Pathways Independent of the Pyrin Inflammasome. |
| المؤلفون: |
Loeven NA, Reuven AD, McGee AP, Dabi C, Mwaura BW, Bliska JB |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 May 20. Date of Electronic Publication: 2024 May 20. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
The Burkholderia cepacia complex contains opportunistic pathogens that cause chronic infections and inflammation in lungs of people with cystic fibrosis. Two closely related species within this complex are Burkholderia cenocepacia and the recently classified Burkholderia orbicola. B. cenocepacia and B. orbicola encode a type VI secretion system and the effector TecA, which is detected by the pyrin/caspase-1 inflammasome, and triggers macrophage inflammatory death. In our earlier study the pyrin inflammasome was dispensable for lung inflammation in mice infected with B. orbicola AU1054, indicating this species activates an alternative pathway of macrophage inflammatory death. Notably, B. cenocepacia J2315 and K56-2 can damage macrophage phagosomes and K56-2 triggers activation of the caspase-11 inflammasome, which detects cytosolic LPS. Here we investigated inflammatory cell death in pyrin-deficient ( Mefv -/- ) mouse macrophages infected with B. cenocepacia J2315 or K56-2 or B. orbicola AU1054 or PC184. Macrophage inflammatory death was measured by cleavage of gasdermin D protein, release of cytokines IL-1α and IL-1β and plasma membrane rupture. Findings suggest that J2315 and K56-2 are detected by the caspase-11 inflammasome in Mefv -/- macrophages, resulting in IL-1β release. In contrast, inflammasome activation is not detected in Mefv -/- macrophages infected with AU1054 or PC184. Instead, AU1054 triggers an alternative macrophage inflammatory death pathway that requires TecA and results in plasma membrane rupture and IL-1α release. Amino acid variation between TecA isoforms in B. cenocepacia and B. orbicola may explain how the latter species triggers a non-inflammasome macrophage death pathway. |
| تواريخ الأحداث: |
Date Created: 20240603 Latest Revision: 20240603 |
| رمز التحديث: |
20240603 |
| مُعرف محوري في PubMed: |
PMC11142134 |
| DOI: |
10.1101/2023.09.28.559184 |
| PMID: |
38826213 |
| قاعدة البيانات: |
MEDLINE |
