Referenced in: none

Automatically associated channels: TRP , TRPC , TRPC1

Title: Helminth induced suppression of macrophage activation is correlated with inhibition of calcium channel activity.

Authors: Arun Chauhan, Yuyang Sun, Biswaranjan Pani, Fredice Quenumzangbe, Jyotika Sharma, Brij B Singh, Bibhuti B Mishra

Journal, date & volume: PLoS ONE, 2014 , 9, e101023

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25013939

Abstract
Helminth parasites cause persistent infections in humans and yet many infected individuals are asymptomatic. Neurocysticercosis (NCC), a disease of the central nervous system (CNS) caused by the cestode Taenia solium, has a long asymptomatic phase correlated with an absence of brain inflammation. However, the mechanisms of immune suppression remain poorly understood. Here we report that murine NCC displays a lack of cell surface maturation markers in infiltrating myeloid cells. Furthermore, soluble parasite ligands (PL) failed to induce maturation of macrophages, and inhibited TLR-induced inflammatory cytokine production. Importantly, PL treatment abolished both LPS and thapsigargin-induced store operated Ca2+ entry (SOCE). Moreover, electrophysiological recordings demonstrated PL-mediated inhibition of LPS or Tg-induced currents that were TRPC1-dependent. Concomitantly STIM1-TRPC1 complex was also impaired that was essential for SOCE and sustained Ca2+ entry. Likewise loss of SOCE due to PL further inhibited NFkB activation. Overall, our results indicate that the negative regulation of agonist induced Ca2+ signaling pathway by parasite ligands may be a novel immune suppressive mechanism to block the initiation of the inflammatory response associated with helminth infections.