During an acute Plasmodium infection, uncontrolled pro-inflammatory responses can result in morbidity and mortality. Regulation of this inflammatory response is required to prevent immunopathology. We therefore decided to investigate a recently characterized subset of regulatory dendritic cells (DCs) that expresses low levels of CD11c and high levels of CD45RB. During a murine Plasmodium yoelii infection, these regulatory CD11cloCD45RB hi DCs become the prevalent CD11c-expressing cells in the spleen, overtaking the conventional CD11chi DCs. Furthermore, the regulatory CD11cloCD45RBhi DCs induce IL-10-expressing CD4 T cells.
In humans, a cell subset expressing a similar phenotype of DC markers – that is CD11cloCD45RBhi – also takes prevalence in the peripheral blood of individuals acutely infected with Plasmodium falciparum. This DC subset appears to also have a regulatory role, as they prevent CD4 T cells from proliferating, even though these T cells are expressing high amounts of IL-2. Moreover these human CD11c loCD45RBhi cells express IL-10 as well as arginase 1, an enzyme that suppresses T cells through the consumption of extracellular L-arginine. Thus the shift towards a DC population with a regulatory phenotype during malaria suggests this is an immunomodulatory mechanism designed to help regulate the immune response during this highly inflammatory disease.
|Commitee:||Lafaille, Juan J., Nardin, Elizabeth H., Raper, Jayne, Sacks, David L.|
|School:||New York University|
|Department:||Basic Medical Science|
|School Location:||United States -- New York|
|Source:||DAI-B 70/07, Dissertation Abstracts International|
|Subjects:||Microbiology, Parasitology, Immunology|
|Keywords:||Inflammation, Malaria, Plasmodium falciparum, Regulatory T cells, Regulatory dendritic cells, T cell suppression|
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