Characterization of immune responses to single or mixed infections with P. yoelii 17XL and P. chabaudi AS in different strains of mice

The outcome of Plasmodium yoelii 17XL (P.y17XL)-infected BALB/c and DBA/2 mice, ranging from death to spontaneous cure, depends largely on the establishment of effective Th1 and Th2 responses and a successful switch between Th1 and Th2 responses, as well as appropriate functioning of CD4+CD25+Foxp3+regulatory T cells (Tregs). The infection with another malaria-causing parasite, Plasmodium chabaudi AS (P.cAS), leads to a different outcome in BALB/c and DBA/2 mice compared to mice infected with P.y17XL alone. To understand the consequence of co-infection with P.y17XL and P.cAS, we determined the proliferation curve of parasites, pro-inflammatory/anti-inflammatory cytokine profiles, and the dynamic changes of the number of Tregs in DBA/2 and BALB/c mice with single or mixed-species infections. The infective mode in mixed-species infections was the same as single P.y17XL infections. The multiplication of P.y17XL parasites prevailed in BALB/c and DBA/2 mice with early mixed infections, as detected by RTQ-PCR. Subsequently, the multiplication of P.cAS parasites dominated in DBA/2 mice with mixed infections, while BALB/c mice succumbed to infection. In addition, the dynamic changes in IFN-γ and IL-4 production in mice with mixed infections, used as a measure of Th1 and Th2 responsiveness, were consistent with P.y17XL-infected mice. Treg activation and the IL-10 level were also closely related to susceptibility to infection. Our findings demonstrate that the characteristics of the immune response during infections with mixed species are dependent on the mode of proliferation of different species of Plasmodium. Indeed, different species of Plasmodium can influence each other in the same host.