title: VCAM-1/α4β1 integrin interaction is crucial for prompt recruitment of immune T cells into the brain during the early stage of reactivation of chronic infection with Toxoplasma gondii to prevent toxoplasmic encephalitis.
abstract: Reactivation of chronic infection with Toxoplasma gondii can cause life-threatening toxoplasmic encephalitis in immunocompromised individuals. We examined the role of VCAM-1/α4β1 integrin interaction in T cell recruitment to prevent reactivation of the infection in the brain. SCID mice were infected and treated with sulfadiazine to establish a chronic infection. VCAM-1 and ICAM-1 were the endothelial adhesion molecules detected on cerebral vessels of the infected SCID and wild-type animals. Immune T cells from infected wild-type mice were treated with anti-α4 integrin or control antibodies and transferred into infected SCID or nude mice, and the animals received the same antibody every other day. Three days later, sulfadiazine was discontinued to initiate reactivation of infection. Expression of mRNAs for CD3δ, CD4, CD8β, gamma interferon (IFN-γ), and inducible nitric oxide synthase (NOS2) (an effector molecule to inhibit T. gondii growth) and the numbers of CD4(+) and CD8(+) T cells in the brain were significantly less in mice treated with anti-α4 integrin antibody than in those treated with control antibody at 3 days after sulfadiazine discontinuation. At 6 days after sulfadiazine discontinuation, cerebral tachyzoite-specific SAG1 mRNA levels and numbers of inflammatory foci associated with tachyzoites were markedly greater in anti-α4 integrin antibody-treated than in control antibody-treated animals, even though IFN-γ and NOS2 mRNA levels were higher in the former than in the latter. These results indicate that VCAM-1/α4β1 integrin interaction is crucial for prompt recruitment of immune T cells and induction of IFN-γ-mediated protective immune responses during the early stage of reactivation of chronic T. gondii infection to control tachyzoite growth.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
authors.forename: Qila
authors.initials: Q
authors.lastname: Sa
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
authors.forename: Eri
authors.initials: E
authors.lastname: Ochiai
authors.affiliation: Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sengoku
authors.affiliation: Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
authors.forename: Melinda E
authors.initials: ME
authors.lastname: Wilson
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
authors.forename: Morgan
authors.initials: M
authors.lastname: Brogli
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Crutcher
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Michie
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Baohui
authors.initials: B
authors.lastname: Xu
authors.affiliation: Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Payne
authors.affiliation: Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
authors.forename: Xisheng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky, USA Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA yasu.suzuki@uky.edu.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000166:cytology; D002908:Chronic Disease; D004660:Encephalitis / Q000276:immunology / Q000469:parasitology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D039041:Integrin alpha4beta1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000145:classification / Q000502:physiology*; D014122:Toxoplasma; D014124:Toxoplasmosis, Animal / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1
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