title: 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.affiliation: Institut de Parasitologie et Pathologie Tropicale, EA 7292, Université de Strasbourg, 3 rue Koeberlé, 67000 Strasbourg, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Sauer
authors.forename: Elise
authors.initials: E
authors.lastname: Rochet
authors.forename: Ibtissem
authors.initials: I
authors.lastname: Lahmar
authors.forename: Julie
authors.initials: J
authors.lastname: Brunet
authors.forename: Marcela
authors.initials: M
authors.lastname: Sabou
authors.forename: Tristan
authors.initials: T
authors.lastname: Bourcier
authors.forename: Ermanno
authors.initials: E
authors.lastname: Candolfi
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Pfaff
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005128:Eye Diseases / Q000276:immunology / Q000469:parasitology*; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*; D014122:Toxoplasma / Q000145:classification; D014124:Toxoplasmosis, Animal / Q000276:immunology*
keywords: Congenital toxoplasmosis; Inflammation; Ocular toxoplasmosis; Retina; T helper cell subsets; Toxoplasma gondii