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Interferon-gamma- and perforin-mediated immune responses for resistance against Toxoplasma gondii in the brain

Published online by Cambridge University Press:  04 October 2011

Yasuhiro Suzuki ,
Qila Sa ,
Marie Gehman  and
Eri Ochiai
Yasuhiro Suzuki*
Affiliation:
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY, USA.
Qila Sa
Affiliation:
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY, USA.
Marie Gehman
Affiliation:
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY, USA.
Eri Ochiai
Affiliation:
Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY, USA.
*
*Corresponding author: Yasuhiro Suzuki, Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA. E-mail: yasu.suzuki@uky.edu
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Abstract

Toxoplasma gondii is an obligate intracellular protozoan parasite that causes various diseases, including lymphadenitis, congenital infection of fetuses and life-threatening toxoplasmic encephalitis in immunocompromised individuals. Interferon-gamma (IFN-γ)-mediated immune responses are essential for controlling tachyzoite proliferation during both acute acquired infection and reactivation of infection in the brain. Both CD4+ and CD8+ T cells produce this cytokine in response to infection, although the latter has more potent protective activity. IFN-γ can activate microglia, astrocytes and macrophages, and these activated cells control the proliferation of tachyzoites using different molecules, depending on cell type and host species. IFN-γ also has a crucial role in the recruitment of T cells into the brain after infection by inducing expression of the adhesion molecule VCAM-1 on cerebrovascular endothelial cells, and chemokines such as CXCL9, CXCL10 and CCL5. A recent study showed that CD8+ T cells are able to remove T. gondii cysts, which represent the stage of the parasite in chronic infection, from the brain through their perforin-mediated activity. Thus, the resistance to cerebral infection with T. gondii requires a coordinated network using both IFN-γ- and perforin-mediated immune responses. Elucidating how these two protective mechanisms function and collaborate in the brain against T. gondii will be crucial in developing a new method to prevent and eradicate this parasitic infection.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 13 , March 2011 , e31
Copyright
Copyright © Cambridge University Press 2011

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References

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Further reading, resources and contacts

Yarovinsky, F. (2008) Toll-like receptors and their role in host resistance to Toxoplasma gondii. Immunology Letters 119, 17-21CrossRefGoogle ScholarPubMed
This article provides an overview on the role of TLRs in resistance to T. gondii infection.Google Scholar
Munoz, M., Liesenfeld, O. and Heimesaat, M.M. (2011) Immunology of Toxoplasma gondii. Immunology Reviews 240, 269-285.CrossRefGoogle ScholarPubMed
This article provides an overview of the immune responses to T. gondii in general, including immune responses in the intestine and those in congenital and ocular toxoplasmosis.Google Scholar
The Toxoplasma gondii database is a genome and functional genomic database in which sequence information is integrated with various genomic-scale data, including community annotation, ESTs, gene expression and proteomics data:http://toxodb.org/toxo/Google Scholar