Dendritic Cells and Their Multiple Roles during Malaria Infection

Abstract

Dendritic cells (DCs) play a central role in the initiation of adaptive immune responses, efficiently presenting antigens to T cells. This ability relies on the presence of numerous surface and intracellular receptors capable of sensing microbial components as well as inflammation and on a very efficient machinery for antigen presentation. In this way, DCs sense the presence of a myriad of pathogens, including Plasmodium spp., the causative agent of malaria. Despite many efforts to control this infection, malaria is still responsible for high rates of morbidity and mortality. Different groups have shown that DCs act during Plasmodium infection, and data suggest that the phenotypically distinct DCs subsets are key factors in the regulation of immunity during infection. In this review, we will discuss the importance of DCs for the induction of immunity against the different stages of Plasmodium, the outcomes of DCs activation, and also what is currently known about Plasmodium components that trigger such activation.

Figure 1

Most common DC surface markers used to differentiate conventional from plasmacytoid DCs and lymphoid tissue/blood from nonlymphoid tissue resident DCs. The colors indicate if a specific marker is expressed only in humans (orange), only in mice (green), or in both (blue) either in humans or in mice. Langerhans cells (LCs) are not represented. Based on [15, 125, 126].

Figure 2

Plasmodium infection activates different DCs subsets. Infection with different stages of Plasmodium activates DCs that in turn start producing proinflammatory (IL-6, IL-12, and TNFα) but also regulatory (IL-10) cytokines. The CD8α ⁺CD11b⁻ DCs are responsible for priming CD8⁺ T cell responses against intrahepatic forms, while both cDCs subsets (CD8α ⁺CD11b⁻ and CD8α ⁺CD11b⁺) play a role in the activation of CD4⁺ T cell responses that can lead to an inflammatory or regulatory outcome, depending on the timing of infection. pDCs also play a role in the induction of a more regulatory CD4⁺ T cell response. The number of BAFF expressing DCs is reduced during Plasmodium infection, and that may reduce their ability to support B cell differentiation directly. Based on [, , –80, 82, 85, 86, 91].