Circulating exosomes may act as a neuroinflammatory mediator in systemic inflammation

Neuroinflammation is implicated in the development and progression of many neurodegenerative diseases. Conditions that lead to a peripheral immune response are often associated with inflammation in the central nervous system (CNS), suggesting a communication between the peripheral immune system and the neuroimmune system. The underlying mechanism of this relationship remains largely unknown; however, experimental studies have demonstrated that exposure to infectious stimuli, such as lipopolysaccharide (LPS) or high-fat diet (HFD) feeding, result in profound peripheral- and neuro-inflammation.

Using the model of endotoxemia with LPS, researchers from the University of Tennessee Health Science Center studied the role of serum-derived exosomes in mediating neuroinflammation. They purified circulating exosomes from the sera of LPS-challenged mice, which were then intravenously injected into normal adult mice.

The researchers found that the recipient mice that received serum-derived exosomes from LPS-challenged mice exhibited elevated microglial activation. Moreover, they observed astrogliosis, increased systemic pro-inflammatory cytokine production, and elevated CNS expression of pro-inflammatory cytokine mRNA and the inflammation-associated microRNA (miR-155) in these recipient mice. Gene expression analysis confirmed that many inflammatory microRNAs were significantly upregulated in the purified exosomes under LPS-challenged conditions. Th e researchers observed accumulated signaling within the microglia of mice that received tail-vein injections of fluorescently labeled exosomes though the percentage of those microglial cells was found low. Finally, purified LPS-stimulated exosomes from blood when infused directly into the cerebral ventricles provoked significant microgliosis and, to a lesser extent, astrogliosis.

Exosomes isolated from LPS-treated mice increase CD68-positive cells


a Photomicrographs of the hippocampal (Hp), neocortical (Cx), and lateral ventricular (LV) areas from C57BL/6J mice. Mice were intravenously injected 1 mg of exosomes (in 200 μl PBS) isolated from the sera of donor mice 6 h after intraperitoneal injection of PBS or 10 mg/kg LPS. The recipient mice were euthanized after 24 h. Brain sections were stained with anti-CD68 antibody (green) and DAPI (blue). Scale bar, 50 μm. b Higher magnification images of the white-dotted box area from a. Figures are presented in the following sequence: upper left, CD68 (green); upper right, Iba1 (red); lower left, merge of CD68 and Iba1; and lower right, DAPI (blue). Co-localization of CD68 and Iba1 (white arrowheads). DG dentate gyrus. Scale bar, 20 μm. c Quantification of CD68-positive cells in the hippocampal, neocortical, and lateral ventricular areas. n = 3–5 per group. Data represent mean ± SEM; *P < 0.05

Li JJ, Wang B, Kodali MC, Chen C, Kim E, Patters BJ, Lan L, Kumar S, Wang X, Yue J, Liao FF. (2018) In vivo evidence for the contribution of peripheral circulating inflammatory exosomes to neuroinflammation. J Neuroinflammation 15(1):8. [article]

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