Infect Immun. 2014 Apr 21. [Epub ahead of print]

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

Sa Q¹, Ochiai E, Sengoku T, Wilson ME, Brogli M, Crutcher S, Michie SA, Xu B, Payne L, Wang X, Suzuki Y.

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 animals received the same antibody every other day. Three days later, sulfadiazine was discontinued to initiate reactivation of infection. Expression of mRNA for CD3δ, CD4, CD8β, IFN-γ, and inducible nitric oxide synthase (NOS2; an effector molecule to inhibit T. gondii growth), and numbers of CD4⁺ and CD8⁺ T cells in the brain, were significantly less in mice treated with anti-α4 integrin antibody than 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 control antibody-treated animals, even though IFN-γ and NOS2 mRNA levels were higher in the former than 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.

PMID:

24752515

[PubMed - as supplied by publisher]