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A motogenic GABAergic system of mononuclear phagocytes facilitates dissemination of coccidian parasites
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.ORCID iD: 0000-0002-7116-0939
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
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Number of Authors: 72020 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 9, article id e60528Article in journal (Refereed) Published
Abstract [en]

Gamma-aminobutyric acid (GABA) serves diverse biological functions in prokaryotes and eukaryotes, including neurotransmission in vertebrates. Yet, the role of GABA in the immune system has remained elusive. Here, a comprehensive characterization of human and murine myeloid mononuclear phagocytes revealed the presence of a conserved and tightly regulated GABAergic machinery with expression of GABA metabolic enzymes and transporters, GABA-A receptors and regulators, and voltage-dependent calcium channels. Infection challenge with the common coccidian parasites Toxoplasma gondii and Neospora caninum activated GABAergic signaling in phagocytes. Using gene silencing and pharmacological modulators in vitro and in vivo in mice, we identify the functional determinants of GABAergic signaling in parasitized phagocytes and demonstrate a link to calcium responses and migratory activation. The findings reveal a regulatory role for a GABAergic signaling machinery in the host-pathogen interplay between phagocytes and invasive coccidian parasites. The co-option of GABA underlies colonization of the host by a Trojan horse mechanism.

Place, publisher, year, edition, pages
2020. Vol. 9, article id e60528
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Biological Sciences
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URN: urn:nbn:se:su:diva-188736DOI: 10.7554/eLife.60528ISI: 000595496600001PubMedID: 33179597OAI: oai:DiVA.org:su-188736DiVA, id: diva2:1519192
Available from: 2021-01-18 Created: 2021-01-18 Last updated: 2022-02-25Bibliographically approved

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Bhandage, Amol K.Olivera, Gabriela C.Kanatani, SachieBarragan, Antonio

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