title: Helminth induced suppression of macrophage activation is correlated with inhibition of calcium channel activity.
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.
authors.affiliation: Department of Basic Sciences, School of Medicine & Health Sciences, The University of North Dakota, Grand Forks, North Dakota, United States of America.
authors.forename: Arun
authors.initials: A
authors.lastname: Chauhan
authors.affiliation: Department of Basic Sciences, School of Medicine & Health Sciences, The University of North Dakota, Grand Forks, North Dakota, United States of America.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Basic Sciences, School of Medicine & Health Sciences, The University of North Dakota, Grand Forks, North Dakota, United States of America.
authors.forename: Biswaranjan
authors.initials: B
authors.lastname: Pani
authors.affiliation: Department of Basic Sciences, School of Medicine & Health Sciences, The University of North Dakota, Grand Forks, North Dakota, United States of America.
authors.forename: Fredice
authors.initials: F
authors.lastname: Quenumzangbe
authors.affiliation: Department of Basic Sciences, School of Medicine & Health Sciences, The University of North Dakota, Grand Forks, North Dakota, United States of America.
authors.forename: Jyotika
authors.initials: J
authors.lastname: Sharma
authors.affiliation: Department of Basic Sciences, School of Medicine & Health Sciences, The University of North Dakota, Grand Forks, North Dakota, United States of America.
authors.forename: Brij B
authors.initials: BB
authors.lastname: Singh
authors.affiliation: Department of Basic Sciences, School of Medicine & Health Sciences, The University of North Dakota, Grand Forks, North Dakota, United States of America.
authors.forename: Bibhuti B
authors.initials: BB
authors.lastname: Mishra
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015220:Calcium Channels / Q000378:metabolism*; D004594:Electrophysiology; D005260:Female; D005455:Fluorescent Antibody Technique; D006376:Helminths / Q000472:pathogenicity*; D047468:Immunoprecipitation; D008262:Macrophage Activation / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020019:Neurocysticercosis / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels / Q000378:metabolism
chemical_list: D015220:Calcium Channels; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1