Trypanosoma cruzi-Infected Human Macrophages Shed Proinflammatory Extracellular Vesicles That Enhance Host-Cell Invasion via Toll-Like Receptor 2

被引：44

作者：

Cronemberger-Andrade, Andre ^{[1
]}

Xander, Patricia ^{[1
]}

Soares, Rodrigo Pedro ^{[2
]}

Pessoa, Natalia Lima ^{[2
]}

Campos, Marco Antonio ^{[2
]}

Ellis, Cameron C. ^{[3
]}

Grajeda, Brian ^{[3
]}

Ofir-Birin, Yifat ^{[4
]}

Almeida, Igor Correia ^{[3
]}

Regev-Rudzki, Neta ^{[4
]}

Torrecilhas, Ana Claudia ^{[1
]}

机构：

[1] Univ Fed Sao Paulo UNIFESP, Dept Ciencias Farmaceut, Sao Paulo, Brazil

[2] FIOCRUZ MG, Inst Rene Rachou, Belo Horizonte, MG, Brazil

[3] Univ Texas El Paso, Dept Biol Sci, Border Biomed Res Ctr, El Paso, TX 79968 USA

[4] Weizmann Inst Sci, Dept Biomol Sci, Rehovot, Israel

来源：

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY | 2020年 / 10卷

基金：

巴西圣保罗研究基金会;

关键词：

Trypanosoma cruzi; toll-like receptor 2; inflammation; extracellular vesicles; macrophage; INTRACELLULAR CA2+; IN-VITRO; EXOSOMES; ACTIVATION; PROTEIN; RESISTANCE; MICE; DIFFERENTIATION; MICROVESICLES; COMMUNICATION;

D O I：

10.3389/fcimb.2020.00099

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Extracellular vesicles (EVs) shed by trypomastigote forms of Trypanosoma cruzi have the ability to interact with host tissues, increase invasion, and modulate the host innate response. In this study, EVs shed from T. cruzi or T.cruzi-infected macrophages were investigated as immunomodulatory agents during the initial steps of infection. Initially, by scanning electron microscopy and nanoparticle tracking analysis, we determined that T. cruzi-infected macrophages release higher numbers of EVs (50-300 nm) as compared to non-infected cells. Using Toll-like-receptor 2 (TLR2)-transfected CHO cells, we observed that pre-incubation of these host cells with parasite-derived EVs led to an increase in the percentage of infected cells. In addition, EVs from parasite or T.cruzi-infected macrophages or not were able to elicit translocation of NF-kappa B by interacting with TLR2, and as a consequence, to alter the EVs the gene expression of proinflammatory cytokines (TNF-alpha, IL-6, and IL-1 beta), and STAT-1 and STAT-3 signaling pathways. By proteomic analysis, we observed highly significant changes in the protein composition between non-infected and infected host cell-derived EVs. Thus, we observed the potential of EVs derived from T. cruzi during infection to maintain the inflammatory response in the host.

引用

页数：15