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Acute and chronic Plasmodium falciparum infections alter the immune competence of the host possibly through changes in dendritic cell (DC) functionality. DCs are the most potent activators of T cells, and migration is integral to their function. Mature DCs express lymphoid chemokine receptors (CCRs), expression of 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 parasite 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 proinflammatory and anti-inflammatory cytokines, such as interleukin-6 (IL-6), IL-10, and tumor necrosis factor alpha, but not IL-12, and induced upregulation 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 parasite-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.

Original publication

DOI

10.1128/IAI.00649-10

Type

Journal article

Journal

Infect Immun

Publication Date

07/2011

Volume

79

Pages

2727 - 2736

Keywords

Antigens, CD, B7-1 Antigen, Cell Movement, Cells, Cultured, Chemokines, Dendritic Cells, Erythrocytes, Hemeproteins, Humans, Immunoglobulins, Interleukin-10, Interleukin-12, Interleukin-6, Lymphocyte Activation, Membrane Glycoproteins, Plasmodium falciparum, Receptors, CXCR4, Tumor Necrosis Factor-alpha, CD83 Antigen