Synergistic Activation of Toll-Like and NOD Receptors by Complementary Antigens as Facilitators of Autoimmune Disease: Review, Model and Novel Predictions

Persistent activation of toll-like receptors (TLR) and nucleotide-binding oligomerization domain-containing proteins (NOD) in the innate immune system is one necessary driver of autoimmune disease (AD), but its mechanism remains obscure. This study compares and contrasts TLR and NOD activation profi...

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Bibliographic Details
Main Author: Robert Root-Bernstein
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:International Journal of Molecular Sciences
Subjects:
TLR
NOD
Online Access:https://www.mdpi.com/1422-0067/21/13/4645
Description
Summary:Persistent activation of toll-like receptors (TLR) and nucleotide-binding oligomerization domain-containing proteins (NOD) in the innate immune system is one necessary driver of autoimmune disease (AD), but its mechanism remains obscure. This study compares and contrasts TLR and NOD activation profiles for four AD (autoimmune myocarditis, myasthenia gravis, multiple sclerosis and rheumatoid arthritis) and their animal models. The failure of current AD theories to explain the disparate TLR/NOD profiles in AD is reviewed and a novel model is presented that explains innate immune support of persistent chronic inflammation in terms of unique combinations of complementary AD-specific antigens stimulating synergistic TLRs and/or NODs. The potential explanatory power of the model is explored through testable, novel predictions concerning TLR- and NOD-related AD animal models and therapies.
ISSN:1661-6596
1422-0067