Suppression of adaptive immunity to heterologous antigens during plasmodium infection through hemozoin-induced failure of dendritic cell function

Owain R. Millington, Caterina Di Lorenzo, R. Stephen Phillips, Paul Garside, James M. Brewer

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117 Citations (Scopus)
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Abstract

Dendritic cells (DCs) are central to the initiation and regulation of the adaptive immune response during infection. Modulation of DC function may therefore allow evasion of the immune system by pathogens. Significant depression of the host's systemic immune response to both concurrent infections and heterologous vaccines has been observed during malaria infection, but the mechanisms underlying this immune hyporesponsiveness are controversial. Here, we demonstrate that the blood stages of malaria infection induce a failure of DC function in vitro and in vivo, causing suboptimal activation of T cells involved in heterologous immune responses. This effect on T-cell activation can be transferred to uninfected recipients by DCs isolated from infected mice. Significantly, T cells activated by these DCs subsequently lack effector function, as demonstrated by a failure to migrate to lymphoid-organ follicles, resulting in an absence of B-cell responses to heterologous antigens. Fractionation studies show that hemozoin, rather than infected erythrocyte (red blood cell) membranes, reproduces the effect of intact infected red blood cells on DCs. Furthermore, hemozoin-containing DCs could be identified in T-cell areas of the spleen in vivo.
Original languageEnglish
Article number5
Number of pages21
JournalJournal of Biology
Volume5
Issue number5
DOIs
Publication statusPublished - 12 Apr 2006

Keywords

  • dendritic cells
  • heterologous antigens
  • Plasmodium infection
  • biophotonics

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