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Helminth Induced Suppression of Macrophage Activation Is Correlated with Inhibition of Calcium Channel Activity
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. Ho...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094426/ https://www.ncbi.nlm.nih.gov/pubmed/25013939 http://dx.doi.org/10.1371/journal.pone.0101023 |
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author | Chauhan, Arun Sun, Yuyang Pani, Biswaranjan Quenumzangbe, Fredice Sharma, Jyotika Singh, Brij B. Mishra, Bibhuti B. |
author_facet | Chauhan, Arun Sun, Yuyang Pani, Biswaranjan Quenumzangbe, Fredice Sharma, Jyotika Singh, Brij B. Mishra, Bibhuti B. |
author_sort | Chauhan, Arun |
collection | PubMed |
description | 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 Ca(2+) 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 Ca(2+) entry. Likewise loss of SOCE due to PL further inhibited NFkB activation. Overall, our results indicate that the negative regulation of agonist induced Ca(2+) signaling pathway by parasite ligands may be a novel immune suppressive mechanism to block the initiation of the inflammatory response associated with helminth infections. |
format | Online Article Text |
id | pubmed-4094426 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40944262014-07-15 Helminth Induced Suppression of Macrophage Activation Is Correlated with Inhibition of Calcium Channel Activity Chauhan, Arun Sun, Yuyang Pani, Biswaranjan Quenumzangbe, Fredice Sharma, Jyotika Singh, Brij B. Mishra, Bibhuti B. PLoS One Research Article 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 Ca(2+) 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 Ca(2+) entry. Likewise loss of SOCE due to PL further inhibited NFkB activation. Overall, our results indicate that the negative regulation of agonist induced Ca(2+) signaling pathway by parasite ligands may be a novel immune suppressive mechanism to block the initiation of the inflammatory response associated with helminth infections. Public Library of Science 2014-07-11 /pmc/articles/PMC4094426/ /pubmed/25013939 http://dx.doi.org/10.1371/journal.pone.0101023 Text en © 2014 Chauhan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Chauhan, Arun Sun, Yuyang Pani, Biswaranjan Quenumzangbe, Fredice Sharma, Jyotika Singh, Brij B. Mishra, Bibhuti B. Helminth Induced Suppression of Macrophage Activation Is Correlated with Inhibition of Calcium Channel Activity |
title | Helminth Induced Suppression of Macrophage Activation Is Correlated with Inhibition of Calcium Channel Activity |
title_full | Helminth Induced Suppression of Macrophage Activation Is Correlated with Inhibition of Calcium Channel Activity |
title_fullStr | Helminth Induced Suppression of Macrophage Activation Is Correlated with Inhibition of Calcium Channel Activity |
title_full_unstemmed | Helminth Induced Suppression of Macrophage Activation Is Correlated with Inhibition of Calcium Channel Activity |
title_short | Helminth Induced Suppression of Macrophage Activation Is Correlated with Inhibition of Calcium Channel Activity |
title_sort | helminth induced suppression of macrophage activation is correlated with inhibition of calcium channel activity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094426/ https://www.ncbi.nlm.nih.gov/pubmed/25013939 http://dx.doi.org/10.1371/journal.pone.0101023 |
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