Host cell manipulation and immunomodulation are important features of obligate intracellular parasites. Yet, the precise mechanisms leading to systemic dissemination of intracellular parasites (acute infection) and life-long persistence in the central nervous system (chronic infection) of the human or animal hosts remain enigmatic.

The processes of host-cell interaction, systemic dissemination and persistence are studied using molecular and cellular experimental approaches and various imaging modalities. Understanding the immune evasion strategies utilized by Toxoplasma and how it orchestrates the subversion of leukocytes may provide key elements of pathogenesis and on the rationale for designing future prophylaxis.

 

Keywords

Apicomplexan parasites, dendritic cells, microglia, cell migration, motility, host-pathogen, GABAergic signalling, biophotonic imaging

 

Dendritic cell (green) infected by Toxoplasma gondii (red)

 

Recent publications

A motogenic GABAergic system of mononuclear phagocytes facilitates dissemination of coccidian parasites. 
Bhandage AK, Olivera GC, Kanatani S, Thompson E, Loré K, Varas-Godoy M, Barragan A.
Elife. 2020 Nov 12;9:e60528. doi: 10.7554/eLife.60528.
PMID: 33179597 Free PMC article.

The unicellular eukaryotic parasite Toxoplasma gondii hijacks the migration machinery of mononuclear phagocytes to promote its dissemination.
Ólafsson EB, Barragan A.
Biol Cell. 2020 Sep;112(9):239-250. doi: 10.1111/boc.202000005. Epub 2020 May 19.
PMID: 32359185 Review.

Convergent Met and voltage-gated Ca2+ channel signaling drives hypermigration of Toxoplasma-infected dendritic cells.
Ólafsson EB, Ten Hoeve AL, Li-Wang X, Westermark L, Varas-Godoy M, Barragan A.
J Cell Sci. 2020 Apr 21;134(5):jcs241752. doi: 10.1242/jcs.241752.
PMID: 32161101

The deubiquitinase OTUB1 augments NF-κB-dependent immune responses in dendritic cells in infection and inflammation by stabilizing UBC13.
Mulas F, Wang X, Song S, Nishanth G, Yi W, Brunn A, Larsen PK, Isermann B, Kalinke U, Barragan A, Naumann M, Deckert M, Schlüter D.
Cell Mol Immunol. 2020 Feb 5. doi: 10.1038/s41423-020-0362-6. Online ahead of print.
PMID: 32024978

Sustained Egr-1 Response via p38 MAP Kinase Signaling Modulates Early Immune Responses of Dendritic Cells Parasitized by Toxoplasma gondii.
Ten Hoeve AL, Hakimi MA, Barragan A.
Front Cell Infect Microbiol. 2019 Oct 11;9:349. doi: 10.3389/fcimb.2019.00349. eCollection 2019.
PMID: 31681626 Free PMC article.

In Vivo CRISPR Screen Identifies TgWIP as a Toxoplasma Modulator of Dendritic Cell Migration. 
Sangaré LO, Ólafsson EB, Wang Y, Yang N, Julien L, Camejo A, Pesavento P, Sidik SM, Lourido S, Barragan A, Saeij JPJ.
Cell Host Microbe. 2019 Oct 9;26(4):478-492.e8. doi: 10.1016/j.chom.2019.09.008.
PMID: 31600500 Free PMC article.

Differential Responses of Bovine Monocyte-Derived Macrophages to Infection by Neospora caninum Isolates of High and Low Virulence.
García-Sánchez M, Jiménez-Pelayo L, Horcajo P, Regidor-Cerrillo J, Ólafsson EB, Bhandage AK, Barragan A, Werling D, Ortega-Mora LM, Collantes-Fernández E.
Front Immunol. 2019 Apr 30;10:915. doi: 10.3389/fimmu.2019.00915. eCollection 2019.
PMID: 31114577 Free PMC article.

Dysregulation of focal adhesion kinase upon Toxoplasma gondii infection facilitates parasite translocation across polarised primary brain endothelial cell monolayers.
Ross EC, Olivera GC, Barragan A.
Cell Microbiol. 2019 Sep;21(9):e13048. doi: 10.1111/cmi.13048. Epub 2019 Jun 27.
PMID: 31099453

Toxoplasma-Induced Hypermigration of Primary Cortical Microglia Implicates GABAergic Signaling. 
Bhandage AK, Kanatani S, Barragan A.
Front Cell Infect Microbiol. 2019 Mar 20;9:73. doi: 10.3389/fcimb.2019.00073. eCollection 2019.
PMID: 30949457 Free PMC article.

Calling in the CaValry-Toxoplasma gondii Hijacks GABAergic Signaling and Voltage-Dependent Calcium Channel Signaling for Trojan horse-Mediated Dissemination. 
Bhandage AK, Barragan A.
Front Cell Infect Microbiol. 2019 Mar 20;9:61. doi: 10.3389/fcimb.2019.00061. eCollection 2019.
PMID: 30949456 Free PMC article. Review.

Advances and Challenges in Understanding Cerebral Toxoplasmosis. 
Schlüter D, Barragan A.
Front Immunol. 2019 Feb 14;10:242. doi: 10.3389/fimmu.2019.00242. eCollection 2019.
PMID: 30873157 Free PMC article. Review.

TIMP-1 promotes hypermigration of Toxoplasma-infected primary dendritic cells via CD63-ITGB1-FAK signaling.
Ólafsson EB, Ross EC, Varas-Godoy M, Barragan A.
J Cell Sci. 2019 Feb 4;132(3):jcs225193. doi: 10.1242/jcs.225193.
PMID: 30635444

Voltage-dependent calcium channel signaling mediates GABAA receptor-induced migratory activation of dendritic cells infected by Toxoplasma gondii.
Kanatani S, Fuks JM, Olafsson EB, Westermark L, Chambers B, Varas-Godoy M, Uhlén P, Barragan A.
PLoS Pathog. 2017 Dec 7;13(12):e1006739. doi: 10.1371/journal.ppat.1006739. eCollection 2017 Dec.
PMID: 29216332 Free PMC article.

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