Pathogenetic immune responses in cerebral malaria

Abstract

In this chapter we will critically review the body of evidence indicating that host immune responses to parasitic infection also play a critical role in cerebral malaria pathogenesis, in addition to parasite-induced pathology. First, in the field of innate immunity, we will discuss the ability of DAMPs and PAMPs to trigger pro-inflammatory responses. Moving on to adaptive immunity, we will underline the importance of the T cell dependency of the neurological syndrome, and will detail the molecules that have been shown essential in this pathogenetic mechanism. The involvement of antigen presenting cells (APC, including monocytes, dendritic cells and their subsets) will be reviewed, with a focus on malarial-associated immunosuppression. The potential importance of antigen processing, co-stimulation and cross-presentation in malarial pathology will also be highlighted. Finally, we will address the potential role of brain endothelial cells as APC and of membrane microparticles as amplifiers of pathology in cerebral malaria.