Regulating the Adaptive Immune Response to Blood-Stage Malaria: Role of Dendritic Cells and CD4⁺Foxp3⁺ Regulatory T Cells

Abstract

Although a clearer understanding of the underlying mechanisms involved in protection and immunopathology during blood-stage malaria has emerged, the mechanisms involved in regulating the adaptive immune response especially those required to maintain a balance between beneficial and deleterious responses remain unclear. Recent evidence suggests the importance of CD11c+ dendritic cells (DC) and CD4+Foxp3+ regulatory T cells in regulating immune responses during infection and autoimmune disease, but information concerning the contribution of these cells to regulating immunity to malaria is limited. Here, we review recent findings from our laboratory and others in experimental models of malaria in mice and in Plasmodium-infected humans on the roles of DC and natural regulatory T cells in regulating adaptive immunity to blood-stage malaria.

Modulation of the Immune and Inflammatory Responses by Plasmodium falciparum Schizont Extracts: Role of Myeloid Dendritic Cells in Effector and Regulatory Functions of CD4 + Lymphocytes

“…The reason we used myeloid dendritic cells as T cell activators instead of circulating monocytes is based on data obtained in experimental models of murine malaria, reporting these cells as the most active antigen-presenting cells (APCs) in the first phase of infection (31); MDDC are described as cells able to influence the development of protective immunity or tolerance dependent on the intensity of the costimulation signals, the affinity of T cells for processed antigens, and, most of all, the cytokine environment in which they operate (6). Furthermore, CD11c ϩ myeloid dendritic cells were shown to be endowed with a greater ability to migrate in the T zone of splenic white pulp than other APCs, such as monocytes/macrophages and B cells (7,8).…”

“…ϩ T cells and B cells (5,6). Therefore, the host's ability to regulate both the magnitude and the timing of antiparasitic inflammatory responses avoiding the development of life-threatening immune-mediated pathology represents the key to the successful resolution of an infection.…”

The C-Type Lectin Receptor DCIR Is Crucial for the Development of Experimental Cerebral Malaria

“…A number of studies indicate that DC functions such as maturation and the ability to cross-present malaria Ags are compromised by the interaction with pRBCs (16)(17)(18), whereas other studies report that DCs from malaria-infected mice are still efficient in presenting pRBC-derived Ags to CD4 + T cells (19,20). In recent years, the contribution of DC subsets to immunity but also malaria-associated pathology has started to be unraveled (21)(22)(23). Nonetheless, little is known about which DC-expressed pattern recognition receptors (PRRs) are involved in host defense to malaria on the one hand and how they might contribute to CM development on the other hand.…”

A Coherent Study on Various Strategies to Combat Malaria.

“…Among these species, P. falciparum causes the most severe form of disease and is responsible for almost all malaria mortality. However, in tropical and subtropical areas, P. vivax can equal P. falciparum as a source of malaria morbidity and is the most widespread species outside Africa [2] in South America and Asia, while infections with P. malariae and P. ovale subspecies are usually mild [3].…”