Hypoacylated LPS from Foodborne Pathogen Campylobacter jejuni Induces Moderate TLR4-Mediated Inflammatory Response in Murine Macrophages

Abstract

Toll-like receptor 4 (TLR4) initiates immune response against Gram-negative bacteria upon specific recognition of lipid A moiety of lipopolysaccharide (LPS), the major component of their cell wall. Some natural differences between LPS variants in their ability to interact with TLR4 may lead to either insufficient activation that may not prevent bacterial growth, or excessive activation which may lead to septic shock. In this study we evaluated the biological activity of LPS isolated from pathogenic strain of Campylobacter jejuni, the most widespread bacterial cause of foodborne diarrhea in humans. With the help of hydrophobic chromatography and MALDI-TOF mass spectrometry we showed that LPS from a C. jejuni strain O2A consists of both hexaacyl and tetraacyl forms. Since such hypoacylation can result in a reduced immune response in humans, we assessed the activity of LPS from C. jejuni in mouse macrophages by measuring its capacity to activate TLR4-mediated proinflammatory cytokine and chemokine production, as well as NFκB-dependent reporter gene transcription. Our data support the hypothesis that LPS acylation correlates with its bioactivity.

Identifying Robust Microbiota Signatures and Interpretable Rules to Distinguish Cancer Subtypes

“…Considering that the breast lactation metabolism is correlated with breast cancer tumorigenesis ( Kim and Wysolmerski, 2016 ; Wani et al, 2017 ), this microorganism is regarded as a potential quantitative parameter for breast cancer. Many studies have identified the infection of Campylobacter in breast cancer ( Korneev et al, 2018 ; Parida and Sharma, 2019 ), further validating the efficacy and the accuracy of our prediction.…”

The Risk G Allele of the Single-Nucleotide Polymorphism rs928413 Creates a CREB1-Binding Site That Activates IL33 Promoter in Lung Epithelial Cells

“…Сells were transfected with 1.8 μg of plasmid DNA and 0.2 μg of pRL-CMV Renilla luciferase control vector using X-treme Gene HP DNA Transfection Reagent (Roche, Basel, Switzerland) according to manufacturer’s protocol. Firefly luciferase activity was measured as described [ 71 ], and normalized to the activity of Renilla luciferase in order to account for the variations in cell transfection and lysis efficiencies.…”

Like Cures Like: Pharmacological Activity of Anti-Inflammatory Lipopolysaccharides From Gut Microbiome

“…(Poxton and Edmond, 1995;d'Hennezel et al, 2017;Jacobson et al, 2018). Another example is the hypoacylated LPS from a foodborne pathogen Campylobacter jejuni that only moderately induces TLR4 dependent immune response (Korneev et al, 2018). Furthermore, Shigella flexneri 2a that contains a mixture of hexaacylated, pentaacylated, and predominantly tetraacylated lipid A in its LPS also significantly decreases its stimulatory effects on NF-kappaB signaling pathway in contrast to the hexaacylated E. coli LPS (Rallabhandi et al, 2008).…”