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PLoS One. 2014 Jul 11;9(7):e101023. doi: 10.1371/journal.pone.0101023. eCollection 2014.

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

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1
Department of Basic Sciences, School of Medicine & Health Sciences, The University of North Dakota, Grand Forks, North Dakota, United States of America.

Erratum in

  • PLoS One. 2014;9(10):e111349.

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.

PMID:
25013939
PMCID:
PMC4094426
DOI:
10.1371/journal.pone.0101023
[Indexed for MEDLINE]
Free PMC Article

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