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

Int J Parasitol. 2013 May 20. pii: S0020-7519(13)00130-6. doi: 10.1016/j.ijpara.2013.04.004. [Epub ahead of print]

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

Sauer A, Rochet E, Lahmar I, Brunet J, Sabou M, Bourcier T, Candolfi E, Pfaff AW.

Institut de Parasitologie et Pathologie Tropicale, EA 7292, Université de Strasbourg, 3 rue Koeberlé, 67000 Strasbourg, France; Service d'Ophtalmologie, Hôpitaux Universitaires de Strasbourg, 1 place de l'Hôpital, 67000 Strasbourg, France.

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.

PMID: 23702129 [PubMed - as supplied by publisher]