Plasmodium suppresses T cell responses to heterologous infections by impairing T cell activation

Malaria is a devastating disease caused by parasites of the genus Plasmodium. Plasmodium falciparum, which is responsible for most malaria related fatalities, suppresses host immune responses during heterologous coinfections or following vaccination. However the mechanisms responsible for this defect are not well defined. The mechanism and to what extent this immunosuppression is occurring was investigated. This study demonstrates that both dendritic cell and T cell activation are impaired following a Plasmodium infection, ultimately altering the adaptive T cell response to secondary infections. T cell suppression is evident early on following a secondary infection and continues throughout the peak of parasitemia. To address the mechanism of Plasmodium T cell suppression of heterologous infections, both T cell activation and expression of costimulatory molecules on dendritic cells were analyzed. It was found that costimulatory molecules on dendritic cells were downregulated, as well as the activation markers CD25 and CD69 on CD8 T cells. These data demonstrate that Plasmodium impairs T cell activation during heterologous infections. These data provide insight into how Plasmodium may be altering immune responses to coinfections in malaria endemic regions and how this could potentially change the administration of vaccines that elicit CD8 T cell responses.