The local immune response to intraocular Toxoplasma re-challenge: less pathology and better parasite control through Treg/Th1/Th2 induction.

Abstract

Ocular toxoplasmosis is a major cause of blindness world-wide. Ocular involvement is frequently seen following congenital infection. Many of these infections are quiescent but pose a life-time risk of reactivation. However, the physiopathology of ocular toxoplasmosis reactivation is largely unexplored. We previously developed a Swiss-Webster outbred mouse model for congenital toxoplasmosis by neonatal injection of Toxoplasma gondii cysts. We also used a mouse model of direct intraocular infection to show a deleterious local T helper 17 type response upon primary infection. In the present study, our two models were combined to study intravitreal re-challenge of neonatally infected mice, as an approximate model of reactivation, in comparison with a primary ocular infection. Using BioPlex proteomic assays in aqueous humour and reverse transcription-PCR for T helper cell transcription factors, we observed diminished T helper 17 type reaction in reinfection, compared with primary infection. In contrast, T helper 2 and T regulatory responses were enhanced. Interestingly, this was also true for T helper 1 markers such as IFN-γ, which was paralleled by better parasite control. Secretion of IL-27, a central cytokine for shifting the immune response from T helper 17 to T helper 1, was also greatly enhanced. We observed a similar protective immune reaction pattern in the eye upon reinfection with the virulent RH strain, with the notable exception of IFN-γ. In summary, our results show that the balance is shifted from T helper 17 to a less pathogenic but more effective anti-parasite Treg/T helper 1/T helper 2 pattern in a reactivation setting.

• Authors: Arnaud Sauer, Elise Rochet, Ibtissem Lahmar, Julie Brunet, Marcela Sabou, Tristan Bourcier, Ermanno Candolfi, Alexander W Pfaff
• Journal: International journal for parasitology (Int J Parasitol) Vol. 43 Issue 9 Pg. 721-8 (Aug 2013) ISSN: 1879-0135 [Electronic] England
• PMID: 23702129 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Topics

• Animals
• Animals, Newborn
• Eye Diseases (immunology, parasitology)
• Mice
• T-Lymphocytes, Regulatory (physiology)
• Th1 Cells (physiology)
• Th2 Cells (physiology)
• Toxoplasma (classification)
• Toxoplasmosis, Animal (immunology)