Toxoplasma gondii infection in the brain inhibits neuronal degeneration and learning and memory impairments in a murine model of Alzheimer's disease.

Sung Joong Lee,Kyoung-Ho Pyo,Young Sang Hwang,Markus M Heimesaat,Eun-Hee Shin,Ki Young Shin,Bong-Kwang Jung,Yoo-Hun Suh,Sang Hyung Lee,Jung-Ho Moon,Hyoungsub Lim,Jong-Yil Chai

doi:10.1371/journal.pone.0033312

Abstract

Immunosuppression is a characteristic feature of Toxoplasma gondii-infected murine hosts. The present study aimed to determine the effect of the immunosuppression induced by T. gondii infection on the pathogenesis and progression of Alzheimer's disease (AD) in Tg2576 AD mice. Mice were infected with a cyst-forming strain (ME49) of T. gondii, and levels of inflammatory mediators (IFN-γ and nitric oxide), anti-inflammatory cytokines (IL-10 and TGF-β), neuronal damage, and β-amyloid plaque deposition were examined in brain tissues and/or in BV-2 microglial cells. In addition, behavioral tests, including the water maze and Y-maze tests, were performed on T. gondii-infected and uninfected Tg2576 mice. Results revealed that whereas the level of IFN-γ was unchanged, the levels of anti-inflammatory cytokines were significantly higher in T. gondii-infected mice than in uninfected mice, and in BV-2 cells treated with T. gondii lysate antigen. Furthermore, nitrite production from primary cultured brain microglial cells and BV-2 cells was reduced by the addition of T. gondii lysate antigen (TLA), and β-amyloid plaque deposition in the cortex and hippocampus of Tg2576 mouse brains was remarkably lower in T. gondii-infected AD mice than in uninfected controls. In addition, water maze and Y-maze test results revealed retarded cognitive capacities in uninfected mice as compared with infected mice. These findings demonstrate the favorable effects of the immunosuppression induced by T. gondii infection on the pathogenesis and progression of AD in Tg2576 mice.

Highlights

Toxoplasma gondii (T. gondii) is a protozoan parasite that commonly infects humans and animals [1]
To determine the neuronal damage caused by T. gondii infection, histopathologic changes in the hippocampal region were examined by hematoxylin and eosin (H-E) staining in Tg2576 Alzheimer’s disease (AD) mice infected or not infected by T. gondii
Because the anti-inflammatory cytokines, IL-10 and TGF-b, are produced by microglial cells for neuroprotection after traumatic injury or stroke [20], we examined the secretion of these cytokines using T. gondii-infected Tg2576 mouse brain tissues (Figure 2B, C) and BV2 cells

Summary

Introduction

Toxoplasma gondii (T. gondii) is a protozoan parasite that commonly infects humans and animals [1]. Humans are generally infected by ingesting oocysts released in cat feces or by consuming undercooked meat containing tissue cysts. Bradyzoites and sporozoites released from cysts and oocysts invade intestinal cells and convert to tachyzoites [1], which when disseminated via blood or the lymphatic system to remote organs induce acute or chronic inflammatory responses. During the chronic stage, the brain is the most commonly affected site [2]. T. gondii is a serious pathogen that can invade vital organs, but usually the infection is mild and asymptomatic in immunocompetent hosts. Normally the infection becomes chronic, remains latent in the brain, and elicits life-long immunity against toxoplasmosis [1]

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