| Author | Ansa-Addo, Ephraim A | |
| Author | Pathak, Paras | |
| Author | McCrossan, Maria V | |
| Author | Rossi, Izadora Volpato | |
| Author | Abdullahi, Mahamed | |
| Author | Stratton, Dan | |
| Author | Lange, Sigrun | |
| Author | Ramirez, Marcel I | |
| Author | Inal, Jameel M | |
| Access date | 2024-12-14T12:12:55Z | |
| Available date | 2024-12-14T12:12:55Z | |
| Document date | 2024 | |
| Citation | ANSA-ADDO, E. A. et al. Monocyte-derived extracellular vesicles, stimulated by Trypanosoma cruzi, enhance cellular invasion in vitro via activated TGF-β1. Journal of Extracellular Vesicles, v. 13, n. e70014, p. 1-24, 2024. | en_US |
| ISSN | 2001-3078 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/67595 | |
| Sponsorship | London Metropolitan University, Grant/Award Number: Quality-Related Research; European Commission, Grant/Award Number: IAPP 612224; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Grant/Award Number: Print; Royal Society, Grant/Award Number: IV0871706/ LMU. | en_US |
| Language | eng | en_US |
| Publisher | WILEY | en_US |
| Rights | open access | en_US |
| Subject in Portuguese | Endocitose | en_US |
| Subject in Portuguese | Vesículas extracelulares | en_US |
| Subject in Portuguese | Trypanosoma cruzi | en_US |
| Title | Monocyte-derived extracellular vesicles, stimulated by Trypanosoma cruzi, enhance cellular invasion in vitro via activated TGF-β1 | en_US |
| Type | Article | en_US |
| DOI | 10.1002/jev2.70014 | |
| Abstract | During cell invasion, large Extracellular Vesicle (lEV) release from host cells was dose-dependently triggered by Trypanosoma cruzi metacyclic trypomastigotes (Mtr). This lEV release was inhibited when IP3-mediated Ca2+ exit from the ER and further Ca2+ entry from plasma membrane channels was blocked, but whilst any store-independent Ca2+ entry (SICE) could continue unabated. That lEV release was equally inhibited if all entry from external sources was blocked by chelation of external Ca2+ points to the major contributor to Mtr-triggered host cell lEV release being IP3/store-mediated Ca2+ release, SICE playing a minor role. Host cell lEVs were released through Mtr interaction with host cell lipid raft domains, integrins, and mechanosensitive ion channels, whereupon [Ca2+]cyt increased (50 to 750 nM) within 15 s. lEV release and cell entry of T. cruzi, which increased up to 30 and 60 mpi, respectively, as well as raised actin depolymerization at 60 mpi, were all reduced by TRPC inhibitor, GsMTx-4. Vesicle release and infection was also reduced with RGD peptide, methyl-β-cyclodextrin, knockdown of calpain and with the calpain inhibitor, calpeptin. Restoration of lEV levels, whether with lEVs from infected or uninfected epithelial cells, did not restore invasion, but supplementation with lEVs from infected monocytes, did. We provide evidence of THP-1 monocyte-derived lEV interaction with Mtr (lipid mixing by R18-dequenching; flow cytometry showing transfer to Mtr of R18 from R18-lEVs and of LAP(TGF-β1). Active, mature TGF-β1 (at 175 pg/×105 in THP-1 lEVs) was detected in concentrated lEV-/cell-free supernatant by western blotting, only after THP-1 lEVs had interacted with Mtr. The TGF-β1 receptor (TβRI) inhibitor, SB-431542, reduced the enhanced cellular invasion due to monocyte-lEVs | en_US |
| Affilliation | London Metropolitan University. School of Human Sciences. Cell Communication in Disease Pathology. London, UK / The Ohio State University. Comprehensive Cancer Center. Department of Internal Medicine. Pelotonia Institute for Immuno-Oncology. Columbus, Ohio, USA. | en_US |
| Affilliation | London Metropolitan University. School of Human Sciences. Cell Communication in Disease Pathology. London, UK / Medical Research Council Harwell. Harwell Science and Innovation Campus. Genotyping Core. Oxfordshire, UK. | en_US |
| Affilliation | London School of Hygiene and Tropical Medicine. Immunology Unit. London, UK. | en_US |
| Affilliation | London Metropolitan University. School of Human Sciences. Cell Communication in Disease Pathology. London, UK / University of Hertfordshire. School of Life and Medical Sciences. Biosciences Research Group. Hatfield, UK / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil / Federal University of Paraná. Postgraduate Program in Cellular and Molecular Biology. Curitiba, PR, Brasil. | en_US |
| Affilliation | London Metropolitan University. School of Human Sciences. Cell Communication in Disease Pathology. London, UK / National Mycobacterium Reference Service-South. Colindale, London, UK. | en_US |
| Affilliation | The Open University. School of Life, Health & Chemical Sciences. Milton Keynes, UK. | en_US |
| Affilliation | University of Westminster. School of Life Sciences. Tissue Architecture and Regeneration Research Group. London, UK / University College London. Institute of Women’s Health. London, UK. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | en_US |
| Affilliation | London Metropolitan University. School of Human Sciences. Cell Communication in Disease Pathology. London, UK / University of Hertfordshire. School of Life and Medical Sciences. Biosciences Research Group. Hatfield, UK. | en_US |
| Subject | Cell uptake | en_US |
| Subject | Endocytosis | en_US |
| Subject | Extracellular vesicles | en_US |
| Subject | Trypanosoma cruzi | en_US |
| DeCS | Trypanosoma cruzi | en_US |
| DeCS | Vesículas extracelulares | en_US |
| DeCS | Endocitose | en_US |
