Endothelial Exosome Plays a Functional Role during Rickettsial Infection.

Autor:	Liu Y; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA., Zhou C; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA., Su Z; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA., Chang Q; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA., Qiu Y; Department of Mathematics and Statistics, Texas Tech University, Lubbock, Texas, USA., Bei J; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA., Gaitas A; The Estelle and Daniel Maggin Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Xiao J; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA., Drelich A; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA., Khanipov K; Department of Pharmacology, University of Texas Medical Branch, Galveston, Texas, USA., Jin Y; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University Medical Campus, Boston, Massachusetts, USA., Golovko G; Department of Pharmacology, University of Texas Medical Branch, Galveston, Texas, USA., Saito TB; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA tais.berellisaito@nih.gov bigong@utmb.edu., Gong B; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA tais.berellisaito@nih.gov bigong@utmb.edu.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2021 May 11; Vol. 12 (3). Date of Electronic Publication: 2021 May 11.
DOI:	10.1128/mBio.00769-21
Abstrakt:	Spotted fever group rickettsioses (SFRs) are devastating human infections. Vascular endothelial cells (ECs) are the primary targets of rickettsial infection. Edema resulting from EC barrier dysfunction occurs in the brain and lungs in most cases of lethal SFR, but the underlying mechanisms remain unclear. The aim of the study was to explore the potential role of Rickettsia -infected, EC-derived exosomes (Exos) during infection. Using size exclusion chromatography (SEC), we purified Exos from conditioned, filtered, bacterium-free media collected from Rickettsia parkeri -infected human umbilical vein ECs (HUVECs) ( R -ECExos) and plasma of Rickettsia australis - or R. parkeri -infected mice ( R -plsExos). We observed that rickettsial infection increased the release of heterogeneous plsExos, but endothelial exosomal size, morphology, and production were not significantly altered following infection. Compared to normal plsExos and ECExos, both R -plsExos and R -ECExos induced dysfunction of recipient normal brain microvascular ECs (BMECs). The effect of R -plsExos on mouse recipient BMEC barrier function is dose dependent. The effect of R -ECExos on human recipient BMEC barrier function is dependent on the exosomal RNA cargo. Next-generation sequencing analysis and stem-loop quantitative reverse transcription-PCR (RT-qPCR) validation revealed that rickettsial infection triggered the selective enrichment of endothelial exosomal mir-23a and mir-30b, which potentially target the endothelial barrier. To our knowledge, this is the first report on the functional role of extracellular vesicles following infection by obligately intracellular bacteria. IMPORTANCE Spotted fever group rickettsioses are devastating human infections. Vascular endothelial cells are the primary targets of infection. Edema resulting from endothelial barrier dysfunction occurs in the brain and lungs in most cases of lethal rickettsioses, but the underlying mechanisms remain unclear. The aim of the study was to explore the potential role of Rickettsia -infected, endothelial cell-derived exosomes during infection. We observed that rickettsial infection increased the release of heterogeneous plasma Exos, but endothelial exosomal size, morphology, and production were not significantly altered following infection. Rickettsia -infected, endothelial cell-derived exosomes induced dysfunction of human recipient normal brain microvascular endothelial cells. The effect is dependent on the exosomal RNA cargo. Next-generation sequencing analysis revealed that rickettsial infection triggered the selective enrichment of endothelial exosomal mir-23a and mir-30b, which potentially target the endothelial barrier. To our knowledge, this is the first report on the functional role of extracellular vesicles following infection by obligately intracellular bacteria. (Copyright © 2021 Liu et al.)
Databáze:	MEDLINE
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