| Schistosomiasis, a chronic, parasitic disease caused by infection with trematode flukes of the genus Schistosoma, is responsible for the greatest mortality within this group. Schistosomiasis is a life-threatening parasitic disease with more than 200 million people infected worldwide.Upon infection, adult worms of S.japonicum produce hundreds of eggs per day and some of these eggs are trapped in the microvasculature of the liver, inducing a strong granulomatous response and associated fibrosis. In the murine model, mice infected with S. japonicum develop an early Thl cytokine response with a severe liver granulomatous inflammatory response. However, the subsequent hepatic fibrosis is due to the chronic production of Th2-type cytokines (e.g. IL-13, IL-4) in response to the parasite eggs. Type-1 responses promote a more pro-inflammatory outcome leading to increased apoptosis, whereas type-2 responses promote gene transcription pathways associated with granuloma formation, collagen synthesis and matrix remodelling.Toxoplasma gondii is an obligate intracellular pathogen from the phylum Apicomplexa and is estimated to infect about one third of the world population. T. gondii is capable of infecting a wide range of mammalian hosts including humans. Most Toxoplasma strains isolated in Europe and North America belong to three distinct clonal lineages, the type I, type II, and type III. These strains differ in virulence in mice and likely cause different sequelae in humans. Previous study has reported that immunizing mice with S. mansoni eggs plus IL-12 before infection to deviate towards Thl immunity, reduces chronic stage fibrosis and acts as an anti-pathology vaccine that prevents scarring without compromising host defense. Based on the distinc M1-polarized immune response induced by type II Toxoplasma strain with polymorphic GRA15Ⅱ and Th2 response in the late stage of disease caused by S. japonicum, the present investigation aims to alleviate the hepatic fibrosis in advanced stage of schistosomiasis through co-infection of T. gondii with S. japonicum. Our work may also contribute to the theoratical and practical approach of host-parasite interaction in both parasitesObjective:To explore the positive effect of overlapping infection of Toxoplasma gondii and Schistosomiasisjaponica on the hepatic fibrosis of mice.Methods:BALB/c mice (specific pathogen free) were transcutaneously infected with (15±2) larvae of Schistosoma japonicum to generate a model of chronic infection after 42～56 days of larval infection, followed by an intragastric infection of 10 cysts T. gondii PRU strain (group Ⅰ). Simultaneously, mice received 10 cysts infection of T. gondii to establish a chronic infection with 35 days, followed by (15±2) larvae infection of S. japonicum (group Ⅱ). Equal number of normal animals were taken as control. Blood and liver tissue samples were collected for HE and Masson staining, respectively. The size of liver egg granulomas and fibrosis areas was measured. Additionally, hyaluronic acid (HA) and hydroxyproline (HYP) in sera were tested.Results:(1) In group Ⅰ, overlapping infection aggravated the mortality rate, but no difference was observed between the two groups.(2) The established chronic infection of schistosomiasis mice, followed by oral reinfection with 10 cysts of Toxoplasma, did not show any inhibitory effects on hepatic fibrotic process (P>0.001).(3) Pre-infection of PRU strain of Toxoplasma before S. japonicum infection resulted in a remarkable amelioration of hepatic fibrosis in mice, presenting the reduced size of egg granulomas and tissue fibrosis (P<0.001). And HA and Hyp levels were significantly decreased in the mice with Toxoplasma pre-infection (P<0.001).Conclusions: Pre-establishment of Thl immune response induced by Toxoplasma may help the animals infected with Schistosoma japonicum to ameliorate the process of hepatic fibrosis. |
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