Characteristics of host immune response associated with pathological injury in BALB/c mice co-infected with plasmodium yoelii 17XL and Plasmodium chabaudi AS

To investigate the relationship between characteristics of immune response and host pathological injury in BALB/c mice co-infected with Plasmodium yoelii 17XL(Py17XL) and Plasmodium chabaudi AS(PcAS).Infections were initiated at the same time by intraperitoneal(i.p.) injection of Py17XL,PcAS,or Py17XL+PcAS parasitized erythrocytes(PE) for each group of BALB/c mice.Parasitemia and mortality were monitored daily.Tail blood collected at different time points was anti-coagulated with heparin on days 3,5,and 8 day post-infection(pi) and centrifuged briefly for DNA extraction using a High Pure Blood Genome DNA Extraction kit.Real-time quantitative(RTQ) PCR was used to determine the parasite burden.On days 0,1,3,5,8,10,12,and 15 pi,splenocyte IFN-γ and IL-4 were dynamically detected with ELISA.Results showed that the level of IFN-γ in BALB/c mice infected with Py 17XL and mice with a mixed infection increased on days 3 and 5 pi,but the level of IFN-γ was three times higher on day 5 pi in mice infected with PcAS compared to other groups of mice.Moreover,the production of IL-4 in the mice infected with Py17XL and mice with a mixed infection peaked on day 8 pi(P0.01) and then slowly declined to a level higher than normal.In BALB/c mice infected with PcAS,the highest IL-4 level appeared on day 10 pi.BALB/c mice infected with PcAS developed only moderate parasitemia that peaked on day 9 pi and then decreased gradually.All mice survived.However,Py17XL was lethal to BALB/c mice on day 5,with a peak parasitemia of 50.57± 9.12%.In contrast,mice infected with mixed species developed a dramatic peak parasitemia on day 5 pi,and all mice died on day 8/9 pi.QRT-PCR data revealed that Py17XL prevailed in BALB/c mice with mixed infections before they died on day 8 pi.These results indicate that protective immunity against malaria infection depends on the establishment of effective Th1 and Th2 responses and a successful switching of immune response from Th1 to Th2.The mode of immune response was closely associated with the degree of pathological injury to the host.The mode of immune response mode in mice infected with Py 17XL was the same as that in mice with a mixed infection.