Abstract
T cells play significant roles during Plasmodium falciparum infections. Their regulation of the immune response in symptomatic children with malaria has been deemed necessary to prevent immune associated pathology. In this study, we phenotypically characterized the expression of T cell inhibitory(PD-1, CTLA-4) and senescent markers (CD28(-), CD57) from children with symptomatic malaria, asymptomatic malaria and healthy controls using flow cytometry. We observed increased expression of T cell exhaustion and senescence markers in the symptomatic children compared to the asymptomatic and healthy controls. T cell senescence markers were more highly expressed on CD8 T cells than on CD4 T cells. Asymptomatically infected children had comparable levels of these markers with healthy controls except for CD8+ PD-1+ T cells which were significantly elevated in the asymptomatic children. Also, using multivariate regression analysis, CTLA-4 was the only marker that could predict parasitaemia level. The results suggest that the upregulation of immune exhaustion and senescence markers during symptomatic malaria may affect the effector function of T cells leading to inefficient clearance of parasites, hence the inability to develop sterile immunity to malaria.
Highlights
Clinical malaria is a disease of public health importance due to its associated morbidity and mortality [1]
We analyzed the pattern of expression of co-inhibitory and senescent markers in children with symptomatic P. falciparum malaria, asymptomatic malaria and healthy controls
We found that the expression of these exhaustive and senescent markers was increased in children with symptomatic malaria compared to those with asymptomatic infections and healthy controls
Summary
Clinical malaria is a disease of public health importance due to its associated morbidity and mortality [1]. Despite promising results of candidate vaccines in naïve individuals, comparatively poorer responses are observed in people in endemic areas [5, 6], indicating that much effort needs to be focused on understanding host factors associated with the development of immunity, especially in malaria-endemic areas. T Cell Exhaustion and Senescence in Malaria clinical symptoms, yet with susceptibility to the infection. This suggests that the naturally induced immune response generated against P. falciparum may not always be potent enough to eradicate the infection. Malaria vaccines that can protect against symptomatic disease and possibly eliminate infections remain a global health priority
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