Non-lethal rodent malarial infection prevents collagen-induced arthritis in mice via anti-arthritic immunomodulation.

AIMS: Immunomodulatory effects of parasitic infections on the outcomes of allergic or autoimmune disorders have been addressed in many experimental studies. We examined the effects of Plasmodium yoelii 17X NL (Py) infection on collagen-induced arthritis (CIA). METHODS AND RESULTS: Male DBA/1J mice were immunized with bovine type II collagen (IIC). Py inoculation was induced at three different time points (1, 4 weeks after or 4 weeks before the immunization). Only the inoculation at 4 weeks after IIC immunization significantly inhibited arthritis development. Non-malarial anaemia induced by phenylhydrazine hydrochloride (PHZ) did not affect arthritis development. In the infected mice, anti-IIC IgG levels were transiently reduced. In addition, splenic production of pro-arthritic cytokines (IL-17 and TNF-α) and IFN-γ decreased, whereas IL-10 production increased. Flow cytometric analysis clarified that the main IL-10 producers in Py-infected mice had the CD4+ CD25- Foxp3- phenotype, presumably Tr1 cells. CONCLUSION: We demonstrated that experimental malarial infection alleviated autoimmune arthritis via immunomodulation, suggesting the importance of malaria in the hygiene hypothesis and the significance of searching for therapeutic immunomodulatory molecules from malarial parasites.

The course of infection with Toxoplasma gondii RH strain in mice pre-vaccinated with gamma irradiated tachyzoites.

Toxoplasma gondii is a ubiquitous protozoan of major medical and veterinary importance. Its treatment is difficult since the available drugs have severe side effects and reactivation may occur anytime. Vaccination with irradiated parasites exhibits ideal characteristics for vaccine development. In our experimental mice model, the protection against challenge with the virulent RH strain was assessed, using 255Gy irradiated tachyzoites. Eighty mice were allocated into 3 groups: naive control group, challenged with virulent RH tachyzoites group and a third group which is challenged with 1 × 106 irradiated tachyzoites, administered as two biweekly doses intraperitoneally. Protection was tested by challenging vaccinated mice with the virulent type RH tachyzoites 30 days after the 2nd vaccination dose. The assessment was built on qualitative clinical, quantitative parasitological, histopathological parameters and measurement of serum Nitric Oxide (NO). The results showed prolonged survival rate, absence of tachyzoites in the peritoneal aspirate by counting, absence of tachyzoites in all examined organs by impression smears, amelioration of histopathological changes in the liver, spleen, brain and lung specimens and increase of the serum NO level in the vaccinated group. Therefore, we propose that irradiated Toxoplasma tachyzoites confer protection for challenged mice and could be an alternative immunization schedule for vaccine development especially for who are at risk of severe immunosuppression.