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Malaria pigment paralyzes dendritic cells.

Urban BC, Todryk S - J. Biol. (2006)

Bottom Line: The capacity of malarial infection to suppress the patient's immune responses both to the parasite and to other antigens has long puzzled researchers.A prime suspect, the parasite-produced pigment hemozoin, has now been clearly shown to mediate immunosuppression by inhibiting dendritic cell activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Old Road, Oxford, OX3 7LJ, UK. britta.urban@ndm.ox.ac.uk

ABSTRACT
The capacity of malarial infection to suppress the patient's immune responses both to the parasite and to other antigens has long puzzled researchers. A prime suspect, the parasite-produced pigment hemozoin, has now been clearly shown to mediate immunosuppression by inhibiting dendritic cell activity.

Show MeSH

Related in: MedlinePlus

Biphasic response of dendritic cells to Plasmodium blood-stage infection in rodents. (a) Early on during infection, engagement of TLR-9 by hemozoin and interaction with infected red blood cells may result in dendritic-cell maturation. Mature dendritic cells present antigen to T cells and induce their activation. Activated T cells proliferate and migrate into primary B-cell follicles where they provide help for antibody production by B cells. (b) With increasing parasitemia, more and more myeloid dendritic cells in the spleen are paralyzed through ingestion of increasing amounts of hemozoin, with negative effects on downstream T-cell and B-cell responses.
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Figure 1: Biphasic response of dendritic cells to Plasmodium blood-stage infection in rodents. (a) Early on during infection, engagement of TLR-9 by hemozoin and interaction with infected red blood cells may result in dendritic-cell maturation. Mature dendritic cells present antigen to T cells and induce their activation. Activated T cells proliferate and migrate into primary B-cell follicles where they provide help for antibody production by B cells. (b) With increasing parasitemia, more and more myeloid dendritic cells in the spleen are paralyzed through ingestion of increasing amounts of hemozoin, with negative effects on downstream T-cell and B-cell responses.

Mentions: Millington et al. [1] then demonstrated, through a series of carefully controlled experiments, that hemozoin acts directly on the dendritic cells and inhibits their maturation in response to maturational stimuli such as LPS or the cell-surface protein CD40 ligand (CD40L). Likewise, CD11c+ dendritic cells isolated from the spleens of infected mice were activated early but not late during infection, and at the later stage were refractory to subsequent stimulation with LPS. Inhibition of dendritic-cell maturation during the late stages of infection had consequences for the initiation of adaptive immune responses: antigen-specific T cells were activated by dendritic cells but failed to proliferate and secrete cytokines. Of particular importance, these T cells did not migrate into B-cell follicles in the spleen to provide the required help to B cells, and so there was also a failure to mount a specific antibody response (Figure 1).


Malaria pigment paralyzes dendritic cells.

Urban BC, Todryk S - J. Biol. (2006)

Biphasic response of dendritic cells to Plasmodium blood-stage infection in rodents. (a) Early on during infection, engagement of TLR-9 by hemozoin and interaction with infected red blood cells may result in dendritic-cell maturation. Mature dendritic cells present antigen to T cells and induce their activation. Activated T cells proliferate and migrate into primary B-cell follicles where they provide help for antibody production by B cells. (b) With increasing parasitemia, more and more myeloid dendritic cells in the spleen are paralyzed through ingestion of increasing amounts of hemozoin, with negative effects on downstream T-cell and B-cell responses.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1561485&req=5

Figure 1: Biphasic response of dendritic cells to Plasmodium blood-stage infection in rodents. (a) Early on during infection, engagement of TLR-9 by hemozoin and interaction with infected red blood cells may result in dendritic-cell maturation. Mature dendritic cells present antigen to T cells and induce their activation. Activated T cells proliferate and migrate into primary B-cell follicles where they provide help for antibody production by B cells. (b) With increasing parasitemia, more and more myeloid dendritic cells in the spleen are paralyzed through ingestion of increasing amounts of hemozoin, with negative effects on downstream T-cell and B-cell responses.
Mentions: Millington et al. [1] then demonstrated, through a series of carefully controlled experiments, that hemozoin acts directly on the dendritic cells and inhibits their maturation in response to maturational stimuli such as LPS or the cell-surface protein CD40 ligand (CD40L). Likewise, CD11c+ dendritic cells isolated from the spleens of infected mice were activated early but not late during infection, and at the later stage were refractory to subsequent stimulation with LPS. Inhibition of dendritic-cell maturation during the late stages of infection had consequences for the initiation of adaptive immune responses: antigen-specific T cells were activated by dendritic cells but failed to proliferate and secrete cytokines. Of particular importance, these T cells did not migrate into B-cell follicles in the spleen to provide the required help to B cells, and so there was also a failure to mount a specific antibody response (Figure 1).

Bottom Line: The capacity of malarial infection to suppress the patient's immune responses both to the parasite and to other antigens has long puzzled researchers.A prime suspect, the parasite-produced pigment hemozoin, has now been clearly shown to mediate immunosuppression by inhibiting dendritic cell activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Old Road, Oxford, OX3 7LJ, UK. britta.urban@ndm.ox.ac.uk

ABSTRACT
The capacity of malarial infection to suppress the patient's immune responses both to the parasite and to other antigens has long puzzled researchers. A prime suspect, the parasite-produced pigment hemozoin, has now been clearly shown to mediate immunosuppression by inhibiting dendritic cell activity.

Show MeSH
Related in: MedlinePlus