Neonatal Immunity to Malaria using a mouse model

Abstract

Abstract High mortality rates caused by malaria are seen in children under five years, but there is limited knowledge on neonatal immunity to the Plasmodium infection due to the lack of a reliable neonatal animal model to study the disease in children. By utilizing a newly developed young rodent model in our lab, we have observed that purified CD4+ T cells from day 14 old young mice (pups) proliferate slower than those purified from 8-week adult mice when stimulated in vitro. To investigate neonatal CD4+ T cell response to malaria, we infected 14-day old pups or adult mice with Plasmodium chabaudi and determined the activation status (CD127−CD44+CD11a+) and differentiation of effector (Teff) subsets, using the expression of CD62L or CD27. Pup CD4+ T cells were activated by downregulating CD127, even though in lower proportions and numbers when compared to adult CD4+ T cells. Surprisingly, there were more proportions of TeffEarly (CD27+CD62L+) and TeffInt (CD27+CD62L−) subsets in the pups than adult mice, which had mostly TeffLate (CD27−CD62L−), suggesting that the transition of Teff subsets is slower in the young mice. We next determined cytokine secretion and Tbet expression by the Teff. Apart from IL-2 which was high in the pups, there was no difference in the proportions of protective cytokines including IFNγ, IL-10 and TNFα in both groups. Effector CD4+ T cells from the pups expressed high proportions of the Tbet transcription factor when compared to adult cells. Taken together, these data suggest that pup CD4 T cells may require more Tbet to differentiate into functional effector cells during Plasmodium infection. Supported by Depart of Biology Appalachian State University