Toxoplasma gondii soluble tachyzoite antigen triggers protective mechanisms against fatal intestinal pathology in oral infection of C57BL/6 mice.

Abstract

Toxoplasma gondii induces a potent IL-12 response early in infection that results in IFN-γ-dependent control of parasite growth. It was previously shown that T. gondii soluble tachyzoite antigen (STAg) injected 48 hr before intraperitoneal infection reduces lipoxin A4 and 5-lipoxygenase (5-LO)-dependent systemic IL-12 and IFN-γ production as well as hepatic immunopathology. This study investigated the ability of STAg-pretreatment to control the fatal intestinal pathology that develops in C57BL/6 mice orally infected with 100 T. gondii cysts. STAg-pretreatment prolonged the animals' survival by decreasing tissue parasitism and pathology, mainly in the ilea. Protection was associated with decreases in the systemic IFN-γ levels and IFN-γ and TNF message levels in the ilea and with increased TGF-β production in this tissue, but protection was independent of 5-LO and IL-4. STAg-pretreatment decreased CD4(+) T cell, NK cell, CD11b(+) monocyte and CD11b(+)CD11c(+) dendritic cell numbers in the lamina propria and increased CD8(+) T cells in the intestinal epithelial compartment. In parallel, decreases were observed in iNOS and IL-17 expression in this organ. These results demonstrate that pretreatment with STAg can induce the recruitment of protective CD8(+) T cells to the intraepithelial compartment and decrease proinflammatory immune mechanisms that promote intestinal pathology in T. gondii infection.

• Authors: Luciana Benevides, Cristina R Cardoso, Cristiane M Milanezi, Letícia S Castro-Filice, Paulo V C Barenco, Romulo O Sousa, Rosangela M Rodrigues, José R Mineo, João S Silva, Neide M Silva
• Journal: PloS one (PLoS One) Vol. 8 Issue 9 Pg. e75138 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24086456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Protozoan
• DNA Primers
• Interleukin-17
• Tumor Necrosis Factor-alpha
• soluble tachyzoite antigen, Toxoplasma gondii
• Interferon-gamma
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse

Topics

• Analysis of Variance
• Animals
• Antigens, Protozoan (immunology, pharmacology)
• DNA Primers (genetics)
• Female
• Flow Cytometry
• Immunity, Cellular (immunology)
• Immunohistochemistry
• Interferon-gamma (immunology)
• Interleukin-17 (immunology)
• Intestines (immunology, parasitology)
• Mice
• Mice, Inbred C57BL
• Nitric Oxide Synthase Type II (immunology)
• Real-Time Polymerase Chain Reaction
• Toxoplasmosis, Animal (immunology, prevention & control)
• Tumor Necrosis Factor-alpha (immunology)