TRP Channels as Sensors of Bacterial Endotoxins.

Brett Boonen,Yeranddy Alpizar,Karel Talavera,Victor Meseguer

doi:10.3390/toxins10080326

Brett Boonen, Yeranddy Alpizar + Show 2 more

Open Access

https://doi.org/10.3390/toxins10080326

Copy DOI

Journal: Toxins	Publication Date: Aug 11, 2018
Citations: 44	License type: CC BY 4.0

Affiliation: VIB-KU Leuven Center for Brain & Disease Research

Abstract

The cellular and systemic effects induced by bacterial lipopolysaccharides (LPS) have been solely attributed to the activation of the Toll-like receptor 4 (TLR4) signalling cascade. However, recent studies have shown that LPS activates several members of the Transient Receptor Potential (TRP) family of cation channels. Indeed, LPS induces activation of the broadly-tuned chemosensor TRPA1 in sensory neurons in a TLR4-independent manner, and genetic ablation of this channel reduced mouse pain and inflammatory responses triggered by LPS and the gustatory-mediated avoidance to LPS in fruit flies. LPS was also shown to activate TRPV4 channels in airway epithelial cells, an effect leading to an immediate production of bactericidal nitric oxide and to an increase in ciliary beat frequency. In this review, we discuss the role of TRP channels as sensors of bacterial endotoxins, and therefore, as crucial players in the timely detection of invading gram-negative bacteria.

Highlights

Immune cells detect infection via specialized pattern recognition receptors that recognize pathogen- and damage-associated molecular patterns (PAMPs and DAMPs)
In addition to the canonical pathway of LPS detection mediated by Toll-like receptor 4 (TLR4), Transient Receptor Potential (TRP) channel-mediated pathways endow sensory neurons and airway epithelial cells with the ability to detect and react to bacterial endotoxins
While several TRP channels present in sensory neurons: TRPA1, TRPV1, TRPM3 and TRPM8, detect LPS, TRPV1 and TRPA1 can account for the majority of the LPS induced neuronal activation

Summary

Introduction

Immune cells detect infection via specialized pattern recognition receptors that recognize pathogen- and damage-associated molecular patterns (PAMPs and DAMPs). Lipoteichoic acids (LTA) and lipopolysaccharides (LPS) are essential building elements of the wall of gram-positive and gram-negative bacteria, respectively These components are released upon bacterial division and lyses and are detected by mammalian cells via Toll-like receptors (TLR) 2 and 4, triggering immune inflammatory responses that eventually clear and kill the invading pathogens [1]. Recent evidence shows that the detection of invading bacteria does not rely entirely on the signalling mechanisms of pattern recognition receptors expressed in immune cells. The interaction of LPS with TLR4 expressed in rat trigeminal neurons was found to sensitize the capsaicin receptor TRPV1, resulting in release of calcitonin gene-related peptide (CGRP) [9,10]. While long-term neuron-related symptoms triggered by LPS are readily explained by activation of TLR4-mediated pathways, the mechanism underlying the acute responses remained unidentified. TRP channels as newly-described players in LPS recognition and acute neuronal and non-neuronal (epithelial) effects, in mammals as well as fruit flies

TRP Channels

Sensory TRP Channels as Effectors of Pathogen-Derived Cues

TRPA1 is A Conserved Bacterial Endotoxin Sensor in Drosophila

Role of Non-Neuronal TRP Channels in LPS Detection

Role of TRP Channels in Other LPS Detection Pathways

Conclusions