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Bacterial pore-forming toxin pneumolysin drives pathogenicity through host extracellular vesicles released during infection
oleh: Saba Parveen, Chinmayi V. Bhat, Aswathy C. Sagilkumar, Shaheena Aziz, J. Arya, Asmita Dutta, Somit Dutta, Sautan Show, Kuldeep Sharma, Sumit Rakshit, John Bernet Johnson, Upendra Nongthomba, Anirban Banerjee, Karthik Subramanian
Format: | Article |
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Diterbitkan: | Elsevier 2024-08-01 |
Deskripsi
Summary: Streptococcus pneumoniae is a global priority respiratory pathogen that kills over a million people annually. The pore-forming cytotoxin, pneumolysin (PLY) is a major virulence factor. Here, we found that recombinant PLY as well as wild-type pneumococcal strains, but not the isogenic PLY mutant, upregulated the shedding of extracellular vesicles (EVs) harboring membrane-bound toxin from human THP-1 monocytes. PLY-EVs induced cytotoxicity and hemolysis dose-dependently upon internalization by recipient monocyte-derived dendritic cells. Proteomics analysis revealed that PLY-EVs are selectively enriched in key inflammatory host proteins such as IFI16, NLRC4, PTX3, and MMP9. EVs shed from PLY-challenged or infected cells induced dendritic cell maturation and primed them to infection. In vivo, zebrafish administered with PLY-EVs showed pericardial edema and mortality. Adoptive transfer of bronchoalveolar-lavage-derived EVs from infected mice to healthy recipients induced lung damage and inflammation in a PLY-dependent manner. Our findings identify that host EVs released during infection mediate pneumococcal pathogenesis.