Pre-existing Schistosoma japonicum infection alters the immune response to Plasmodium berghei infection in C57BL/6 mice.

Mei-lian Wang,En-jie Luo,Ya-ming Cao,Ya-jun Guo,Ying Zhang

doi:10.1186/1475-2875-12-322

Abstract

BackgroundSince helminths and malaria parasites are often co-endemic, it is important to clarify the immunoregulatory mechanism that occurs during the process of co-infection. A previous study confirmed that dendritic cells (DCs) are involved in the establishment and regulation of the T-cell-mediated immune response to malaria infection. In the current study, distinct response profiles for splenic DCs and regulatory T cell (Treg) responses were assessed to evaluate the effects of a pre-existing Schistosoma japonicum infection on malaria infection.MethodsMalaria parasitaemia, survival rate, brain histopathology and clinical experimental cerebral malaria (ECM) were assessed in both Plasmodium berghei ANKA-mono-infected and S. japonicum-P. berghei ANKA-co-infected mice. Cell surface/intracellular staining and flow cytometry were used to analyse the level of splenic DC subpopulations, toll-like receptors (TLRs), DC surface molecules, Tregs (CD4+CD25+Foxp3+), IFN-γ/IL-10-secreting Tregs, and IFN-γ+/IL-10+-Foxp3-CD4+ T cells. IFN-γ, IL-4, IL-5, IL-10 and IL-13 levels were determined in splenocyte supernatants using enzyme-linked immunosorbent assay (ELISA).ResultsThe co-infected mice had significantly higher malaria parasitaemia, compared with the mono-infected mice, on days 2, 3, 7 and 8 after P. berghei ANKA infection. Mono-infected mice had a slightly lower survival rate, while clinical ECM symptoms, and brain pathology, were significantly more severe during the period of susceptibility to ECM. On days 5 and 8 post P. berghei ANKA infection, co-infected mice had significantly lower levels of CD11c+CD11b+, CD11c+CD45R/B220+, CD11c+TLR4+, CD11c+TLR9+, CD11c+MHCII+, CD11c+CD86+, IFN-γ-secreting Tregs, and IFN-γ+Foxp3-CD4+ T cells in single-cell suspensions of splenocytes when compared with P. berghei ANKA-mono-infected mice. Co-infected mice also had significantly lower levels of IFN-γ and higher levels of IL-4, IL-5, and IL-13 in splenocyte supernatants compared to mono-infected mice. There were no differences in the levels of IL-10-secreting Tregs or IL-10+Foxp3-CD4+ T cells between co-infected and mono-infected mice.ConclusionsA Tregs-associated Th2 response plays an important role in protecting against ECM pathology. Pre-existing S. japonicum infection suppressed TLR ligand-induced DC maturation and had an anti-inflammatory effect during malaria infection not only by virtue of its ability to induce Th2 responses, but also by directly suppressing the ability of DC to produce pro-inflammatory mediators.

Highlights

Since helminths and malaria parasites are often co-endemic, it is important to clarify the immunoregulatory mechanism that occurs during the process of co-infection
The mice were randomly assigned to three groups. 25 mice were infected with P. berghei Plasmodium berghei ANKA (ANKA) (P. berghei ANKA-mono-infection group), 15 mice were infected with S. japonicum. (S. japonicum-mono-infection group), and 25 mice were infected with both S. japonicum and P. berghei ANKA
Parasitaemia, survival rate and disease assessment of Experimental cerebral malaria (ECM) Malaria parasitaemia (Figure 1A), mortality (Figure 1B) and ECM scores (Figure 1C) were recorded daily in the P. berghei ANKA-mono-infection mice and the coinfection group mice and comparisons of these were made between the 2 groups

Summary

Introduction

Since helminths and malaria parasites are often co-endemic, it is important to clarify the immunoregulatory mechanism that occurs during the process of co-infection. Malaria is an infectious disease caused by the Plasmodium parasite that continues to be a health issue for humans. It is one of the most common pathogenic factors of morbidity and mortality in sub-Saharan Africa [1]. The prominent pathogenesis of cerebral malaria (CM) is adherence and sequestration of parasitized red blood cells (pRBCs), immune cells and platelets to the vascular endothelial cells lining the small blood vessels of the brain. This leads to microhaemorrhages and oedema in the brain [3,4]

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