AUTHOR=Bhandage Amol K. , Barragan Antonio 

TITLE=Calling in the CaValry—Toxoplasma gondii Hijacks GABAergic Signaling and Voltage-Dependent Calcium Channel Signaling for Trojan horse-Mediated Dissemination

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2019.00061

DOI=10.3389/fcimb.2019.00061

ISSN=2235-2988

ABSTRACT=<p>Dendritic cells (DCs) are regarded as the gatekeepers of the immune system but can also mediate systemic dissemination of the obligate intracellular parasite <italic>Toxoplasma gondii</italic>. Here, we review the current knowledge on how <italic>T. gondii</italic> hijacks the migratory machinery of DCs and microglia. Shortly after active invasion by the parasite, infected cells synthesize and secrete the neurotransmitter γ-aminobutyric acid (GABA) and activate GABA-A receptors, which sets on a hypermigratory phenotype in parasitized DCs <italic>in vitro</italic> and <italic>in vivo</italic>. The signaling molecule calcium plays a central role for this migratory activation as signal transduction following GABAergic activation is mediated via the L-type voltage-dependent calcium channel (L-VDCC) subtype Ca<sub>v</sub>1.3. These studies have revealed that DCs possess a GABA/L-VDCC/Ca<sub>v</sub>1.3 motogenic signaling axis that triggers migratory activation upon <italic>T. gondii</italic> infection. Moreover, GABAergic migration can cooperate with chemotactic responses. Additionally, the parasite-derived protein Tg14-3-3 has been associated with hypermigration of DCs and microglia. We discuss the interference of <italic>T. gondii</italic> infection with host cell signaling pathways that regulate migration. Altogether, <italic>T. gondii</italic> hijacks non-canonical signaling pathways in infected immune cells to modulate their migratory properties, and thereby promote its own dissemination.</p>