Inhibition of Borrelia Burgdorferi-Induced TLR2-NFκB Canonical Signaling by Gallic Acid through Targeting the CD14+ Adaptor Protein and p65 Molecule.

Abstract

The cases of Lyme disease caused by Borrelia burgdorferi infection have been increasing throughout Northern America and Europe. This pathogen, if not treated in a timely manner with antibiotics, can cause persisting and debilitating health outcomes. In the search for novel agents against B. burgdorferi, we investigated a phenolic compound-gallic acid-for its anti-Borrelia and anti-inflammatory effects. Our results showed its biocidal effect starting from 100 μg/mL against active spirochetes, persisters/round-shaped bodies, and biofilm like aggregates of B. burgdorferi sensu stricto. Activation of macrophages by live B. burgdorferi also resulted in a robust NFκB-dependent proinflammatory responses seen in increased production of cytokines. Using human CD14+ macrophages in vitro, we showed that CD14+ adaptor and phosphorylated p65 molecule are impeded at nonbiocidal and noncytotoxic concentrations of gallic acid, resulting in the inhibition of both expression and secretion of cytokines IL1β, IL6, and TNFα. Our findings demonstrate efficacy of gallic acid against B. burgdorferi and provide potential mechanistic insight into its TLR2/CD14+-NFκB mediated mode of action. Further studies on the potential of gallic acid as a safe and effective compound against Borrelia-caused infection are warranted.

• Authors: Anna Goc, Matthias Rath, Aleksandra Niedzwiecki
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 19 (Sep 20 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 36232290 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Anti-Inflammatory Agents
• Cytokines
• Interleukin-6
• Lipopolysaccharide Receptors
• NF-kappa B
• TLR2 protein, human
• Toll-Like Receptor 2
• Tumor Necrosis Factor-alpha
• Gallic Acid

Topics

• Anti-Bacterial Agents (metabolism, pharmacology)
• Anti-Inflammatory Agents (metabolism)
• Borrelia burgdorferi
• Cytokines (metabolism)
• Gallic Acid (metabolism, pharmacology)
• Humans
• Interleukin-6 (metabolism)
• Lipopolysaccharide Receptors (immunology)
• Lyme Disease (drug therapy)
• NF-kappa B (metabolism)
• Toll-Like Receptor 2 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)