Adaptive immune responses mediated age-related Plasmodium yoelii 17XL and 17XNL infections in 4 and 8-week-old BALB/c mice.

Backgroud: It is important to expound the opposite clinical outcomes between children and adulthood for eradicate malaria. There remains unknown about the correlation between adaptive immune response and age-related in malaria.
Methods: 4 and 8-week-old mice were used to mimic children and adulthood, respectively. Parasitemia and the survival rate were monitored. The proportion and function of Th1 and Th2 cells were detected by FACS. The levels of IFN-γ, IL-4, total IgG, IgG1, IgG2a and Plasmodium yoelii MSP-1-specific IgG were measured by ELISA.
Results: The adult group showed greater resistance to P. yoelii 17XL infection, with lower parasitemia. Compared with 4-week-old mice, the percentage of CD4 ⁺ T-bet ⁺ IFN-γ ⁺ Th1 cells as well as IFN-γ production were significantly increased on day 5 p.i. in the 8-week-old mice after P. yoelii 17XNL infection. The percentage of CD4 ⁺ GATA3 ⁺ IL-4 ⁺ Th2 cells and CD4 ⁺ CXCR5 ⁺ Tfh cells, and IL-4 production in the 8-week-old mice significantly increased on day 5 and day 10 after P. yoelii 17XNL infection. Notably, the levels of total IgG, IgG1, IgG2a and P. yoelii MSP-1-specific IgG were also significantly increased in the 8-week-old mice. PD-1, a marker of exhaustion, was up-regulated on CD4 ⁺ or activated CD4 ⁺ T cells in the 8-week-old mice as compared to the 4-week-old group.
Conclusions: Thus, we consider that enhanced cellular and humoral adaptive immunity might contribute to rapid clearance of malaria among adults, likely in a PD-1-dependent manner due to induction of CD4 ⁺ T cells exhaustion in P. yoelii 17XNL infected 8-week-old mice.