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

Authors

Qila Sa, University of KentuckyFollow
Eri Ochiai, University of Kentucky
Tomoko Sengoku, University of KentuckyFollow
Melinda E. Wilson, University of KentuckyFollow
Morgan Brogli, University of Kentucky
Stephen Crutcher, University of Kentucky
Sara A. Michie, Stanford University
Baohui Xu, Stanford University
Laura Payne, Virginia Polytechnic Institute and State University
Xisheng Wang, Virginia Polytechnic Institute and State University
Yasuhiro Suzuki, University of KentuckyFollow

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.

Document Type

Article

Publication Date

7-2014

Notes/Citation Information

Published in Infection and Immunity, v. 82, no. 7, p. 2826-2839.

Copyright © 2014, American Society for Microbiology. All Rights Reserved.

The copyright holders have granted the permission for posting the article here.

Digital Object Identifier (DOI)

http://dx.doi.org/10.1128/IAI.01494-13

Funding Information

This work was supported in part by grants from the National Institutes of Health (AI078756, AI095032, and AI077887 to Y.S.) and a grant (08R-2047 to Y.S.) from the Stanley Medical Research Institute.

Repository Citation

Sa, Qila; Ochiai, Eri; Sengoku, Tomoko; Wilson, Melinda E.; Brogli, Morgan; Crutcher, Stephen; Michie, Sara A.; Xu, Baohui; Payne, Laura; Wang, Xisheng; and Suzuki, Yasuhiro, "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" (2014). Microbiology, Immunology, and Molecular Genetics Faculty Publications. 69.
https://uknowledge.uky.edu/microbio_facpub/69