An
infection of mice with Plasmodium chabaudi is characterized by a rapid and marked inflammatory response with a rapid but regulated production of
interleukin-12 (IL-12),
tumor necrosis factor-alpha (
TNF-alpha), and
interferon-gamma (IFN-gamma). Recent studies have shown that dendritic cells (DCs) are activated in vivo in the spleen, are able to process and present
malaria antigens during
infection, and may provide a source of
cytokines that contribute to polarization of the CD4 T-cell response. P. chabaudi-infected erythrocytes are phagocytosed by DCs, and
peptides of
malaria proteins are presented on major histocompatibility complex (MHC) class II. The complex
disulfide-bonded structure of some
malaria proteins can impede their processing in DCs, which may affect the magnitude of the CD4 T-cell response and influence T-helper 1 (Th1) or Th2 polarization. DCs exhibit a wide range of responses to parasite-infected erythrocytes depending on their source, their maturational state, and the Plasmodium species or strain. P. chabaudi-infected erythrocytes stimulate an increase in the expression of costimulatory molecules and MHC class II on mouse bone marrow-derived DCs, and they are able to induce the production of pro-inflammatory
cytokines such as
IL-12,
TNF-alpha, and
IL-6, thus enhancing the Th1 response of naïve T cells. IFN-gamma and
TNF-alpha play a role in both protective immunity and the pathology of the
infection, and the inflammatory disease may be regulated by
IL-10 and
transforming growth factor-beta. It will therefore be important to elucidate the host and parasite molecules that are involved in activation or suppression of the DCs and to understand the interplay between these opposing forces on the host response in vivo during a
malaria infection.