Age-related susceptibility and resistance to nonlethal Plasmodium yoelii infection in C57BL/6 mice

Abstract

In cases of human malaria, children suffer very high rates of morbidity and mortality. To analyse the mechanisms involved in age-dependent protection against malaria, we investigated the characterization of immune responses to Plasmodium yoelii 17XNL (P.y 17XNL) in young (3 weeks) and middle-aged (8 months) C57BL/6 mice. In this study, we found that 100% of young mice succumbed to P.y 17XNL infection with higher parasitemia, while middle-aged mice were able to clear blood parasites and no mortality was observed. These observations suggested that the young C57BL/6 mice were susceptible to P.y 17XNL infection, whereas the middle-aged mice were resistant. Cellular analysis revealed that both the numbers of splenic myeloid dendritic cells (mDCs) as well as the expression of DC maturation markers were higher in middle-aged mice than those in young mice. The numbers of IgG1- or IgG2asecreting B cells increased markedly in middle-aged mice after infection with P.y 17XNL. The dynamic change of the number of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in mice infected with P.y 17XNL was also different between the two groups. In addition, the levels of IFN-? and NO increased in both groups during early parasite infection, while there was also an obvious increase in IL-4 production in the infected middle-aged mice. The change in IL -10 levels following infection was consistent with that of the change in the number of Tregs. The survival of middle-aged mice following P.y 17XNL infection was dependent upon the establishment of effective Th1 and Th2 responses and a successful switch between Th1 and Th2 responses, as well as appropriate functioning of Tregs. © Institute of Parasitology, Biology Centre ASCR.