Endosomal Toll-Like Receptors Intermediate Negative Impacts of Viral Diseases, Autoimmune Diseases, and Inflammatory Immune Responses on the Cardiovascular System Publisher Pubmed



Tabatabaei FS^{1, 2} ; Shafeghat M^{2, 3, 4} ; Azimi A¹ ; Akrami A⁵ ; Rezaei N^{2, 4, 6}
Source: Expert Review of Clinical Immunology Published:2025

Abstract

Introduction: Cardiovascular disease (CVD) is the leading cause of morbidity globally, with chronic inflammation as a key modifiable risk factor. Toll-like receptors (TLRs), pivotal components of the innate immune system, including TLR-3, −7, −8, and −9 within endosomes, trigger intracellular cascades, leading to inflammatory cytokine production by various cell types, contributing to systemic inflammation and atherosclerosis. Recent research highlights the role of endosomal TLRs in recognizing self-derived nucleic acids during sterile inflammation, implicated in autoimmune conditions like myocarditis. Areas covered: This review explores the impact of endosomal TLRs on viral infections, autoimmunity, and inflammatory responses, shedding light on their intricate involvement in cardiovascular health and disease by examining literature on TLR-mediated mechanisms and their roles in CVD pathophysiology. Expert opinion: Removal of endosomal TLRs mitigates myocardial damage and immune reactions, applicable in myocardial injury. Targeting TLRs with agonists enhances innate immunity against fatal viruses, lowering viral loads and mortality. Prophylactic TLR agonist administration upregulates TLRs, protecting against fatal viruses and improving survival. TLRs play a complex role in CVDs like atherosclerosis and myocarditis, with therapeutic potential in modulating TLR reactions for cardiovascular health. © 2024 Informa UK Limited, trading as Taylor & Francis Group.