Acute and chronic Plasmodium falciparum infections alter the immune competence of the host possibly through changes in dendritic cell functionality. Dendritic cells (DCs) are the most potent activators of T cells and migration is integral to their function. Mature DCs express lymphoid chemokine receptors (CCRs) which enables them to migrate to the lymph nodes where they encounter naïve T cells. The present study aimed to investigate the impact of the synthetic analog to malaria pigment hemozoin, i.e. β-hematin, or infected erythrocytes (iRBCs) on the activation status of human monocyte-derived DCs and on their expression of CCRs. Human monocyte-derived DCs partially matured upon incubation with β-hematin as indicated by an increased expression of CD80 and CD83. Both β-hematin and iRBCs provoked the release of pro-inflammatory and anti-inflammatory cytokines such as IL-6, IL-10 and TNF-α, but not IL-12, and induced up-regulation of the lymphoid chemokine receptor CXCR4, which was coupled to an increased migration to lymphoid ligands. Taken together, these results suggest that the partial and transient maturation of human myeloid DCs upon stimulation with malaria-derived products and the increased IL-10, but lack of IL-12 secretion, may lead to suboptimal activation of T cells. This may in turn lead to impaired adaptive immune responses and therefore insufficient clearance of the parasites.

Plasmodium falciparum-infected erythrocytes and {beta}-hematin induce partial maturation of human dendritic cells and increase their migratory ability in response to lymphoid chemokines.

TINTI, ANNA;VARANI, STEFANIA
2011

Abstract

Acute and chronic Plasmodium falciparum infections alter the immune competence of the host possibly through changes in dendritic cell functionality. Dendritic cells (DCs) are the most potent activators of T cells and migration is integral to their function. Mature DCs express lymphoid chemokine receptors (CCRs) which enables them to migrate to the lymph nodes where they encounter naïve T cells. The present study aimed to investigate the impact of the synthetic analog to malaria pigment hemozoin, i.e. β-hematin, or infected erythrocytes (iRBCs) on the activation status of human monocyte-derived DCs and on their expression of CCRs. Human monocyte-derived DCs partially matured upon incubation with β-hematin as indicated by an increased expression of CD80 and CD83. Both β-hematin and iRBCs provoked the release of pro-inflammatory and anti-inflammatory cytokines such as IL-6, IL-10 and TNF-α, but not IL-12, and induced up-regulation of the lymphoid chemokine receptor CXCR4, which was coupled to an increased migration to lymphoid ligands. Taken together, these results suggest that the partial and transient maturation of human myeloid DCs upon stimulation with malaria-derived products and the increased IL-10, but lack of IL-12 secretion, may lead to suboptimal activation of T cells. This may in turn lead to impaired adaptive immune responses and therefore insufficient clearance of the parasites.
Giusti P.; Urban B.C.; Frascaroli G.; Albrecht L.; Tinti A.; Troye-Blomberg M.; Varani S.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/102490
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