%0 Journal Article
%T Voltage-dependent calcium channel signaling mediates GABAA receptor-induced migratory activation of dendritic cells infected by Toxoplasma gondii
%A Antonio Barragan
%A Benedict Chambers
%A Einar B. Olafsson
%A Jonas M. Fuks
%A Linda Westermark
%A Manuel Varas-Godoy
%A Per Uhl¨¦n
%A Sachie Kanatani
%J -
%D 2017
%R 10.1371/journal.ppat.1006739
%X The obligate intracellular parasite Toxoplasma gondii exploits cells of the immune system to disseminate. Upon T. gondii-infection, ¦Ã¨Caminobutyric acid (GABA)/GABAA receptor signaling triggers a hypermigratory phenotype in dendritic cells (DCs) by unknown signal transduction pathways. Here, we demonstrate that calcium (Ca2+) signaling in DCs is indispensable for T. gondii-induced DC hypermotility and transmigration in vitro. We report that activation of GABAA receptors by GABA induces transient Ca2+ entry in DCs. Murine bone marrow-derived DCs preferentially expressed the L-type voltage-dependent Ca2+ channel (VDCC) subtype Cav1.3. Silencing of Cav1.3 by short hairpin RNA or selective pharmacological antagonism of VDCCs abolished the Toxoplasma-induced hypermigratory phenotype. In a mouse model of toxoplasmosis, VDCC inhibition of adoptively transferred Toxoplasma-infected DCs delayed the appearance of cell-associated parasites in the blood circulation and reduced parasite dissemination to target organs. The present data establish that T. gondii-induced hypermigration of DCs requires signaling via VDCCs and that Ca2+ acts as a second messenger to GABAergic signaling via the VDCC Cav1.3. The findings define a novel motility-related signaling axis in DCs and unveil that interneurons and DCs share common GABAergic motogenic pathways. T. gondii employs GABAergic non-canonical pathways to induce host cell migration and facilitate dissemination
%K Parasitic diseases
%K Toxoplasma gondii
%K Tachyzoites
%K Gamma-aminobutyric acid
%K Spleen
%K Jaw
%K Blood
%K Cell membranes
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006739