Dendritic Cells from Malaria-Infected Mice Are Fully Functional APC

Abstract

Malaria infection has long been associated with diminished T cell responses in vitro and more recently in experimental studies in vivo. Suppression of T cell-proliferative responses during malaria has been attributed to macrophages in a variety of murine and human systems. More recently, however, attention has been directed at the role of dendritic cells in this phenomenon, with several studies suggesting that maturation of dendritic cells is inhibited in vitro by the presence of malaria-infected E. In the studies reported here, we have examined the function of dendritic cells taken directly from infected mice. We found that they express high levels of costimulatory proteins and class II MHC, can activate naive T cells to produce IL-2 as efficiently as dendritic cells from uninfected mice, and support high levels of IFN-γ production by naive T cells through an IL-12-dependent mechanism. Dendritic cells from infected mice also support higher levels of TNF-α production by naive T cells. These same dendritic cells present parasite Ag to a malaria-specific T cell hybridoma, a finding that demonstrates that dendritic cells participate in the generation of Ag-specific immunity during infection. Our findings challenge the contention that dendritic cell function is inhibited by malaria infection.

Role of TGF‐β and PGE2 in T cell responses during Plasmodium yoelii infection

“…1G). This probably explains why others have not found this CD11c + cell-mediated inhibitory effect on T cells in mice during early infection [41]. We also found a CD8 + T cell inhibitory activity in the incubation media of CD11c -cells at day 5 of infection, that may be related to the one described for CD4 + T cells [42].…”

Systemic Tumor Necrosis Factor Generated during Lethal Plasmodium Infections Impairs Dendritic Cell Function

“…Studies have found that dendritic cell (DC) 3 function is compromised during Plasmodium falciparum infections and suggested that this was a factor in the pathogenesis of severe disease (1,2). Similarly, studies of rodent P. berghei infections have also found that DC functions are compromised following infection (3)(4)(5) but other studies have found that DCs from mice infected with P. chabaudi or P. yoelii were fully functional (6,7).…”

Cutting Edge: The Acquisition of TLR Tolerance during Malaria Infection Impacts T Cell Activation

“…We therefore hypothesized that the DCs isolated from mice during acute infection would stimulate high levels of IFN-␥ by responding T cells, but DCs isolated later would preferentially stimulate activation of anti-inflammatory T cells. In previous studies, we established the first part of this hypothesis by showing that DCs isolated from day 6 after infection with P. yoelii stimulate high levels of IFN-␥ by naive T cells in an IL-12-dependent manner (11). In this study, we have investigated the function of DCs isolated from later stages of infection.…”