Jacob R. Greenmyer, Robert A. Gaultney, Catherine A. Brissette, John A. Watt
Abstract
The Lyme disease causing bacterium Borrelia burgdorferi has an affinity for the central nervous system (CNS) and has been isolated from human cerebral spinal fluid by 18 days following Ixodes scapularis tick bite. Signaling from resident immune cells of the CNS could enhance CNS penetration by B. burgdorferi and activated immune cells through the blood brain barrier resulting in multiple neurological complications, collectively termed neuroborreliosis. The ensuing symptoms of neurological impairment likely arise from a glial-driven, host inflammatory response to B. burgdorferi. To date, however, the mechanism by which the bacterium initiates neuroinflammation leading to neural dysfunction remains unclear. We hypothesized that dead B. burgdorferi and bacterial debris persist in the CNS in spite of antibiotic treatment and contribute to the continuing inflammatory response in the CNS. To test our hypothesis, cultures of primary human microglia were incubated with live, antibiotic-killed and antibiotic-killed sonicated B. burgdorferi to define the response of microglia to different forms of the bacterium. We demonstrate that primary human microglia treated with B. burgdorferi show increased expression of pattern recognition receptors and genes known to be involved with cytoskeletal rearrangement and phagocytosis including MARCO, SCARB1, PLA2, PLD2, CD14, and TLR3. In addition, we observed increased expression and secretion of pro-inflammatory mediators and neurotrophic factors such as IL-6, IL-8, CXCL-1, and CXCL-10. Our data also indicate that B. burgdorferi interacts with the cell surface of primary human microglia and may be internalized following this initial interaction. Furthermore, our results indicate that dead and sonicated forms of B. burgdorferi induce a significantly larger inflammatory response than live bacteria. Our results support our hypothesis and provide evidence that microglia contribute to the damaging inflammatory events associated with neuroborreliosis.
This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 February 2021.
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#3,276,403
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Outputs from Frontiers in Microbiology
#2,914
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Outputs of similar age
#63,104
of 332,598 outputs
Outputs of similar age from Frontiers in Microbiology
#99
of 605 outputs
Altmetric has tracked 25,218,929 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 28,929 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.5. This one has done well, scoring higher than 89% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 332,598 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 81% of its contemporaries.
We're also able to compare this research output to 605 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 83% of its contemporaries.
