Dendritic cells, pro-inflammatory responses, and antigen presentation in a rodent malaria infection.
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.
Langhorne
Jean
J
Division of Parasitology, National Institute for Medical Research, London, UK. jlangho@nimr.mrc.ac.uk
Albano
Frank R
FR
Hensmann
Meike
M
Sanni
Latifu
L
Cadman
Emma
E
Voisine
Cecile
C
Sponaas
Anne-Marit
AM
D000818:Animals; D017951:Antigen Presentation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D007249:Inflammation / Q000276:immunology* / Q000469:parasitology / Q000503:physiopathology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016788:Plasmodium chabaudi / Q000276:immunology*