TY - JOUR
T1 - Trypanosoma cruzi-Infected Human Macrophages Shed Proinflammatory Extracellular Vesicles That Enhance Host-Cell Invasion via Toll-Like Receptor 2
AU - Cronemberger-Andrade, Andre
AU - Xander, Patricia
AU - Soares, Rodrigo Pedro
AU - Pessoa, Natalia Lima
AU - Campos, Marco Antonio
AU - Ellis, Cameron C.
AU - Grajeda, Brian
AU - Ofir-Birin, Yifat
AU - Almeida, Igor Correia
AU - Regev-Rudzki, Neta
AU - Torrecilhas, Ana Claudia
N1 - We thank all colleagues from Laboratório de Imunologia Celular & Bioquímica de fungos e protozoários (LICBfp), Departamento de Ciências Farmacêuticas, UNIFESP who provided helpful technical advice and expertise that greatly assisted the research. This work was supported by the FAPESP (2016-01917-3) and doctoral fellowship from CNPq and CAPES. IA was partially supported by the grant No. 2G12MD007592 from the National Institute of General Medical Sciences (NIGMS). We are grateful to the Biomolecule Analysis Core Facility (BACF) at UTEP/BBRC, funded by NIGMS grant No. 2G12MD007592, for the access to the LC-MS instrument. Author contributions - AC-A, PX, IA, YO-B, NR-R, and AT conceived and designed the experiments. AC-A, PX, YO-B, and AT performed most experiments. NP and MC assisted in NF-κB translocation assay. IA, CE, and BG performed the proteomic analysis. AC-A, PX, YO-B, and AT wrote the manuscript. AC-A, PX, RS, YO-B, IA, NR-R, and AT contributed to final manuscript. All the authors reviewed the manuscript
PY - 2020/3/20
Y1 - 2020/3/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85083046017&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fcimb.2020.00099
DO - https://doi.org/10.3389/fcimb.2020.00099
M3 - مقالة
SN - 2235-2988
VL - 10
JO - Frontiers in Cellular and Infection Microbiology
JF - Frontiers in Cellular and Infection Microbiology
M1 - 99
ER -