Efficient control of Plasmodium yoelii infection in BALB/c and C57BL/6 mice with pre-existing Strongyloides ratti infection.

About 225 million malaria cases have been reported worldwide in 2009, and one-third of the world's population is infected with parasitic helminths. As helminths and Plasmodium are co-endemic, concurrent infections frequently occur. Helminths have been shown to modulate the host's immune response; therefore, pre-existing helminth infections may interfere with the efficient immune response to Plasmodium. To study the interaction between helminths and Plasmodium, we established a murine model of co-infection using the gastrointestinal nematode Strongyloides ratti and Plasmodium yoelii. We show that a pre-existing Strongyloides infection slightly enhanced peak parasitemia and weight loss in P. yoelii-infected BALB/c mice, while disease progression was not altered in co-infected C57BL/6 mice. The Plasmodium-induced IFN-γ production and final clearance of Plasmodium infection were not affected by S. ratti co-infection in both C57BL/6 and BALB/c mice. Interestingly, the T helper cell (Th) 2 response induced by S. ratti was significantly suppressed upon P. yoelii co-infection. This suppressed Th2 response, however, was still sufficient to allow expulsion of S. ratti parasitic adults. Taken together, we provide evidence that simultaneous presence of helminth and protist parasites does not interfere with efficient host defence in our co-infection model although changes in Th responses were observed.

Efficient control of Leishmania and Strongyloides despite partial suppression of nematode-induced Th2 response in co-infected mice.

Endemic regions for the pathogenic nematode Strongyloides and parasitic protist Leishmania overlap and therefore co-infections with both parasites frequently occur. As the Th2 and Th1 immune responses necessary to efficiently control Strongyloides and Leishmania infections are known to counterregulate each other, we analysed the outcome of co-infection in the murine system. Here, we show that Leishmania major-specific Th1 responses partially suppressed the nematode-induced Th2 response in co-infected mice. Despite this modulation, successful expulsion of gut dwelling Strongyloides was not suppressed in mice with pre-existing or subsequent Leishmania infection. A pre-existing Strongyloides infection, in contrast, did not interfere with efficient type-1 responses but even increased pro-inflammatory cytokine production. Also, control of L. major infections was not affected by pre-existing nematode infection. Taken together, we provide evidence that simultaneous presence of helminth and protist parasites did not interfere with efficient host defence in our co-infection model.

Strongyloides ratti infection induces transient nematode-specific Th2 response and reciprocal suppression of IFN-gamma production in mice.

Over one-third of the world population is infected with parasitic helminths, Strongyloides ssp. accounting for approximately 30-100 million infected people. In this study, we employ the experimental system of murine Strongyloides ratti infection to investigate the interaction of this pathogenic nematode with its mammalian host. We provide a comprehensive kinetic description of the immune response to S. ratti infection that was reflected by induction of antigen-specific IgM and IgG1, mast cell activation and a Th2-like cytokine response. T cells derived from infected mice displayed an increased IL-3, IL-4, IL-5, IL-13 and IL-10 response to CD3-engagement in comparison with T cells derived from naïve mice. The IFN-gamma response to CD3-engagement that was well detectable in T cells derived from naïve mice, however, was suppressed in T cells derived from infected mice. Both, the induction of the S. ratti-specific Th2 response and the suppression of pro-inflammatory cytokines were transient and observed in strict correlation to the course of infection and the number of infective larvae used. Finally, comparing artificial infections induced by subcutaneous injection of larvae to natural infections, we observed similar antigen-specific T cell responses although the natural infection led to a significantly lower worm burden.