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Published on: June 23, 2013
Lipopolysaccharide-mediated macrophage polarization, conserved pathogenesis, and implications for peripheral
Leah Elson1, Niels Eijkelkamp2, J Henk Coert2
1University Medical Center Utrecht, Room Number G04.126, P.O. Box 85060, 3508 AB, Utrecht, Netherlands. l.c.elson@umcutrecht.nl.
Objective And Design:
This systematic review synthesized evidence for a conserved lipopolysaccharide (LPS)-mediated pathogenic mechanism across diverse tissues and evaluated its potential relevance to peripheral neuropathy.
Methods:
Studies were identified in which LPS was the independent exposure and pro-inflammatory, M1-like macrophage activation/polarization was an outcome. Structured evidence mapping was used to code in-vivo studies for direct measurement of prespecified steps along a proposed pathway: gut perturbation→barrier disruption→circulating LPS→systemic inflammation→tissue interface disruption→innate immune activation→M1-like macrophage skew→tissue dysfunction. Conditional concordance and downstream chain completeness scores were calculated.
Results:
Mechanistic patterns were conserved between pulmonary, cardiac, renal, lymphatic, gastrointestinal, central nervous, adipose, osseous, urologic, dental, hepatic, uterine, and pancreatic tissues. Conditional concordance with the proposed pathway was high (mean 0.984 ± 0.053). Eleven studies assessed all downstream steps from LPS exposure to tissue dysfunction, each demonstrating full chain completeness. M1 macrophage skew (87%), innate immune activation (87%), and circulating LPS (82.6%) were the most frequently reported steps.
Conclusions:
These findings demonstrate conservation of LPS-driven M1-like macrophage polarization and tissue injury across systems, supporting the need to further investigate the biological plausibility of a gut-immune-nerve axis contributing to peripheral neuropathy.
Insights
Lipopolysaccharide (LPS) drives similar tissue injury pathways across the body, involving M1 macrophage activation. This conserved mechanism may contribute to peripheral neuropathy, warranting further investigation into the gut-immune-nerve axis.
Area of Science:
- Immunology
- Pathology
- Neuroscience
Background:
- Lipopolysaccharide (LPS) is a key component of Gram-negative bacteria.
- LPS can trigger pro-inflammatory responses and tissue damage.
- The conserved mechanisms of LPS-mediated pathology across different tissues are not fully understood.
Purpose of the Study:
- To systematically review evidence for a conserved LPS-mediated pathogenic mechanism across diverse tissues.
- To evaluate the relevance of this conserved mechanism to peripheral neuropathy.
Main Methods:
- Systematic review of in-vivo studies with LPS exposure and M1-like macrophage activation as outcomes.
- Structured evidence mapping to assess a proposed pathway from gut perturbation to tissue dysfunction.
- Calculation of conditional concordance and downstream chain completeness scores.
Main Results:
- Mechanistic patterns of LPS-mediated pathology were conserved across 14 different tissue types.
- High conditional concordance (mean 0.984) with the proposed pathway was observed.
- Eleven studies demonstrated full chain completeness from LPS exposure to tissue dysfunction, with M1 macrophage skew (87%) being a frequent outcome.
Conclusions:
- LPS-driven M1-like macrophage polarization and tissue injury are conserved across multiple organ systems.
- These findings support further investigation into a gut-immune-nerve axis in the context of peripheral neuropathy.
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