Direct activation of dendritic cells by the malaria parasite,Plasmodium chabaudi chabaudi

Seixas, Elsa; Cross, Caroline; Quin, Stuart; Langhorne, Jean

doi:10.1002/1521-4141(2001010)31:10<2970::aid-immu2970>3.0.co;2-s

Cited by 84 publications

(70 citation statements)

References 40 publications

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“…Both studies showed that when DCs are matured in vitro in the presence of infected E, they express lower levels of class II MHC and costimulatory proteins and provide poorer stimulation for T cells than control DCs. By contrast, our results (13) as well as those of Seixas et al (14) found increased levels of class II MHC and costimulatory proteins on DCs during both P. yoelii infection and interaction with P. chabaudi, although neither study tested the ability of DCs to activate naive T cells.…”

contrasting

confidence: 94%

Dendritic Cells from Malaria-Infected Mice Are Fully Functional APC

Perry

Rush

Wilson

et al. 2004

The Journal of Immunology

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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.

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confidence: 94%

Dendritic Cells from Malaria-Infected Mice Are Fully Functional APC

Perry

Rush

Wilson

et al. 2004

The Journal of Immunology

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“…In mouse models of malaria, DCs are thought to play an important role in the induction of Th1-dependent immune responses that are protective against bloodstage malaria infection (2,6,9). In the present study, we describe a new flow cytometry technique we developed to measure levels of phagocytosis of pRBCs and nRBCs by mouse BM-derived or spleen DCs in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies using mouse models of malaria have provided evidence for an important role of DCs in inducing protective immunity to blood-stage malaria. Plasmodium chabaudi chabaudi schizonts were found to induce bone marrow (BM)-derived DCs to express MHC class II and costimulatory molecules and to produce IL-12, TNF-␣, and IL-6 (6). In mice infected with P. chabaudi, CD11c ϩ DCs were observed to migrate from the marginal zone of the spleen to the CD4 ϩ T cell-rich periarteriolar lymphoid sheath and to exhibit up-regulated expression of costimulatory molecules as well as increased production of IFN-␥ (7).…”

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confidence: 99%

Interaction of Mouse Dendritic Cells and Malaria-Infected Erythrocytes: Uptake, Maturation, and Antigen Presentation

Ing

Segura

Thawani

et al. 2006

The Journal of Immunology

117

104

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Consistent with their seminal role in detecting infection, both mouse bone marrow-derived and splenic CD11c+ dendritic cells (DCs) exhibited higher levels of uptake of Plasmodium chabaudi-parasitized RBCs (pRBCs) than of noninfected RBCs (nRBCs) as determined by our newly developed flow cytometric technique using the dye CFSE to label RBCs before coculture with DCs. To confirm that expression of CFSE by CD11c+ cells following coculture with CFSE-labeled pRBCs represents internalization of pRBC by DCs, we showed colocalization of CFSE-labeled pRBCs and PE-labeled CD11c+ DCs by confocal fluorescence microscopy. Treatment of DCs with cytochalasin D significantly inhibited the uptake of pRBCs, demonstrating that uptake is an actin-dependent phagocytic process. The uptake of pRBCs by splenic CD11c+ DCs was significantly enhanced after infection in vivo and was associated with the induction of DC maturation, IL-12 production, and stimulation of CD4+ T cell proliferation and IFN-γ production. These results suggest that DCs selectively phagocytose pRBCs and present pRBC-derived Ags to CD4+ T cells, thereby promoting development of protective Th1-dependent immune responses to blood-stage malaria infection.

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“…Antigen-presenting cells (APCs) produce interleukin 12 (IL-12), IL-15, IL-18, and tumor necrosis factor alpha (TNF-␣) (17,26,31,32,37,38,40,44,45,48), which can rapidly activate cells of the innate immune system to produce gamma interferon (IFN-␥) (31,32,44,64). After several days (around 5 days in mice), IFN-␥ from ␣␤ T cells begins to dominate the response.…”

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confidence: 99%

Macrophage-Mediated but Gamma Interferon-Independent Innate Immune Responses Control the Primary Wave ofPlasmodium yoeliiParasitemia

et al. 2007

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In most models of blood-stage malaria infection, proinflammatory immune responses are required for control of infection and elimination of parasites. We hypothesized therefore that the fulminant infections caused in mice by the lethal strain of Plasmodium yoelii (17XL) might be due to failure to activate a sufficient inflammatory response. Here we have compared the adaptive CD4 ؉ T-cell and innate immune response to P. yoelii 17XL with that induced by the self-resolving, nonlethal strain of P. yoelii, 17X(NL). During the first 7 to 9 days of infection, splenic effector CD4 ؉ T-cell responses were similar in mice with lethal and nonlethal infections with similar levels of activation in vivo and equivalent proliferation in vitro following mitogenic stimulation. Nonspecific T-cell hyporesponsiveness was observed at similar levels during both infections and was due, in part, to suppression mediated by CD11b ؉ cells. Importantly, however, RAG ؊/؊ mice were able to control the initial growth phase of nonlethal P. yoelii infection as effectively as wild-type mice, indicating that T cells and/or B cells play little, if any, role in control of the primary peak of parasitemia. Somewhat unexpectedly, we could find no clear role for either NK cells or gamma interferon (IFN-␥) in controlling primary P. yoelii infection. In contrast, depletion of monocytes/macrophages exacerbated parasite growth and anemia during both lethal and nonlethal acute P. yoelii infections, indicating that there is an IFN-␥-, NK cell-, and T-cell-independent pathway for induction of effector macrophages during acute malaria infection.

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Direct activation of dendritic cells by the malaria parasite,Plasmodium chabaudi chabaudi

Cited by 84 publications

References 40 publications

Dendritic Cells from Malaria-Infected Mice Are Fully Functional APC

Dendritic Cells from Malaria-Infected Mice Are Fully Functional APC

Interaction of Mouse Dendritic Cells and Malaria-Infected Erythrocytes: Uptake, Maturation, and Antigen Presentation

Macrophage-Mediated but Gamma Interferon-Independent Innate Immune Responses Control the Primary Wave ofPlasmodium yoeliiParasitemia

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