Intracellular TLR7 is activated in human oligodendrocytes in response to Borrelia burgdorferi exposure. (3rd April 2018)

• Record Type: Journal Article
• Authors: Parthasarathy, Geetha; Philipp, Mario T.
• Is Part Of: Neuroscience letters. Volume 671(2018)
• Page Start: 38
• Page End: 42
• Publication Date: 2018-04-03
• Subjects: Toll-like receptor -- Oligodendrocytes -- Innate immunity -- Lyme neuroborreliosis; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2018.01.058
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Inflammation has a causal role in B. burgdorferi mediated pathogenesis. Intracellular TLR7 contributes to B. burgdorferi induced immunity in oligodendrocytes. This indicates a novel possible niche for bacteria, or uptake of ligands by novel pathways. Abstract: Lyme neuroborreliosis, caused by the gram-negative bacterium Borrelia burgdorferi, may affect the central and/or peripheral nervous systems. In previous studies, we showed that human oligodendrocytes exposed to the bacteria undergo apoptosis in an inflammatory environment, and that inflammatory pathways trigger cell-death pathways. We further demonstrated that several receptor tyrosine kinases were involved in triggering downstream effects, leading to inflammation and apoptosis. Toll-like receptors TLR2 and TLR5, which are commonly studied receptors in Lyme disease, only had a minimal role in inflammatory processes. To delineate the role of other TLRs, if any, real-time RT-PCR array experiments were carried out as an initial screen. Along with several inflammatory genes, TLR7 mRNA was upregulated in cells exposed to B. burgdorferi . Further analysis by immunohistochemistry showed that the TLR7 protein is present in readily detectable amounts, although no discernible differences could be seen between medium and B. burgdorferi -exposed cells by this technique. Nevertheless, use of specific inhibitors and siRNA showed that TLR7 is involved in inducing IL-6 and CCL2 in a dose dependent manner, and likely CXCL8. Triggering an intracellular receptor such as TLR7, which senses RNA, in typically non-phagocytic oligodendrocytes indicates either a niche for the bacterium inside the cell or novel uptake of nucleic acids to initiate inflammatory responses.