Monocyte-derived extracellular vesicles, stimulated by Trypanosoma cruzi, enhance cellular invasion in vitro via activated TGF-β1

被引：0

作者：

Ansa-Addo, Ephraim A. ^{[1
,2
]}

Pathak, Paras ^{[1
,3
]}

Mccrossan, Maria V. ^{[4
]}

Rossi, Izadora Volpato ^{[1
,5
,6
,7
]}

Abdullahi, Mahamed ^{[1
,8
]}

Stratton, Dan ^{[9
]}

Lange, Sigrun ^{[10
,11
]}

Ramirez, Marcel I. ^{[6
]}

Inal, Jameel M. ^{[1
,5
]}

机构：

[1] London Metropolitan Univ, Sch Human Sci, Cell Commun Dis Pathol, London N7 8DB, England

[2] Ohio State Univ, Pelotonia Inst Immuno Oncol, Comprehens Canc Ctr, Dept Internal Med, Columbus, OH USA

[3] Genotyping Core, Med Res Council Harwell, Harwell Sci & Innovat Campus, Harwell Sci & Innovat Campus, Didcot OX11 0RD, Oxon, England

[4] London Sch Hyg & Trop Med, Immunol Unit, London, England

[5] Univ Hertfordshire, Sch Life & Med Sci, Biosci Res Grp, Hatfield, England

[6] Fundacao Oswaldo Cruz FIOCRUZ PR, Inst Carlos Chagas, Curitiba, Brazil

[7] Univ Fed Parana, Postgrad Program Cellular & Mol Biol, Curitiba, Brazil

[8] Natl Mycobacterium Reference Serv South NMRS South, London, England

[9] Open Univ, Sch Life Hlth & Chem Sci, Milton Keynes, England

[10] Univ Westminster, Sch Life Sci, Tissue Architecture & Regenerat Res Grp, London, England

[11] UCL, Inst Womens Hlth, London, England

来源：

JOURNAL OF EXTRACELLULAR VESICLES | 2024年 / 13卷 / 11期

关键词：

cell uptake; endocytosis; extracellular vesicles; Trypanosoma cruzi; GROWTH-FACTOR-BETA; ACTIN CYTOSKELETON; CEREBRAL MALARIA; DENDRITIC CELLS; CALCIUM-ENTRY; MICROVESICLES; EXOSOMES; PATHWAY; SURFACE; RECEPTOR;

D O I：

10.1002/jev2.70014

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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-beta-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-beta 1). Active, mature TGF-beta 1 (at 175 pg/x105 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-beta 1 receptor (T beta RI) inhibitor, SB-431542, reduced the enhanced cellular invasion due to monocyte-lEVs.

引用

页数：24