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Updated: May 11, 2026

Detection of Neu1 Sialidase Activity in Regulating TOLL-like Receptor Activation
Published on: September 7, 2010
Campylobacter jejuni lipooligosaccharide sialylation, phosphorylation, and amide/ester linkage modifications
Holly N Stephenson1, Constance M John, Neveda Naz
1Infectious Diseases and Microbiology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom.
Abstract:
Campylobacter jejuni is a leading cause of acute gastroenteritis. C. jejuni lipooligosaccharide (LOS) is a potent activator of Toll-like receptor (TLR) 4-mediated innate immunity. Structural variations of the LOS have been previously reported in the oligosaccharide (OS) moiety, the disaccharide lipid A (LA) backbone, and the phosphorylation of the LA. Here, we studied LOS structural variation between C. jejuni strains associated with different ecological sources and analyzed their ability to activate TLR4 function. MALDI-TOF MS was performed to characterize structural variation in both the OS and LA among 15 different C. jejuni isolates. Cytokine induction in THP-1 cells and primary monocytes was correlated with LOS structural variation in each strain. Additionally, structural variation was correlated with the source of each strain. OS sialylation, increasing abundance of LA d-glucosamine versus 2,3-diamino-2,3-dideoxy-d-glucose, and phosphorylation status all correlated with TLR4 activation as measured in THP-1 cells and monocytes. Importantly, LOS-induced inflammatory responses were similar to those elicited by live bacteria, highlighting the prominent contribution of the LOS component in driving host immunity. OS sialylation status but not LA structure showed significant association with strains clustering with livestock sources. Our study highlights how variations in three structural components of C. jejuni LOS alter TLR4 activation and consequent monocyte activation.
Insights
Campylobacter jejuni lipooligosaccharide (LOS) structure variations significantly impact Toll-like receptor 4 (TLR4) activation. Specific structural changes in LOS correlate with immune cell responses and bacterial source, particularly in livestock-associated strains.
Area of Science:
- Microbiology
- Immunology
- Structural Biology
Background:
- Campylobacter jejuni is a primary cause of bacterial gastroenteritis.
- C. jejuni lipooligosaccharide (LOS) activates innate immunity via Toll-like receptor 4 (TLR4).
- Previous studies identified structural variations in C. jejuni LOS, including the oligosaccharide (OS) and lipid A (LA) moieties.
Purpose of the Study:
- To investigate LOS structural variations in C. jejuni strains from diverse ecological sources.
- To analyze the impact of these structural variations on TLR4 activation.
- To correlate LOS structure with bacterial ecological origin.
Main Methods:
- MALDI-TOF MS was used to characterize LOS structural variations in 15 C. jejuni isolates.
- Cytokine induction was measured in THP-1 cells and primary human monocytes.
- LOS structural features were correlated with TLR4 activation levels and bacterial source.
Main Results:
- Structural variations in OS sialylation, LA composition, and phosphorylation correlated with TLR4 activation.
- LOS-induced inflammatory responses mimicked those of live C. jejuni bacteria.
- OS sialylation, but not LA structure, was associated with livestock-associated C. jejuni strains.
Conclusions:
- Variations in C. jejuni LOS structure, specifically OS sialylation, LA, and phosphorylation, modulate TLR4 activation and subsequent immune responses.
- LOS is a key bacterial component driving host immunity during C. jejuni infection.
- Ecological source influences C. jejuni LOS structure, with implications for host-pathogen interactions.
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