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Parasite-Dependent Expansion of TNF Receptor II- Positive Regulatory T Cells with Enhanced Suppressive Activity in Adults with Severe Malaria.
- Source :
- PLoS Pathogens; Apr2009, Vol. 5 Issue 4, p1-10, 10p, 1 Chart, 4 Graphs
- Publication Year :
- 2009
-
Abstract
- Severe Plasmodium falciparum malaria is a major cause of global mortality, yet the immunological factors underlying progression to severe disease remain unclear. CD4<superscript>+</superscript>CD25<superscript>+</superscript> regulatory T cells (Treg cells) are associated with impaired T cell control of Plasmodium spp infection. We investigated the relationship between Treg cells, parasite biomass, and P. falciparum malaria disease severity in adults living in a malaria-endemic region of Indonesia. CD4<superscript>+</superscript>CD25<superscript>+</superscript>Foxp3<superscript>+</superscript>CD127<superscript>lo</superscript> Treg cells were significantly elevated in patients with uncomplicated (UM; n = 17) and severe malaria (SM; n = 16) relative to exposed asymptomatic controls (AC; n = 10). In patients with SM, Treg cell frequency correlated positively with parasitemia (r = 0.79, p = 0.0003) and total parasite biomass (r = 0.87, p < 0.001), both major determinants for the development of severe and fatal malaria, and Treg cells were significantly increased in hyperparasitemia. There was a further significant correlation between Treg cell frequency and plasma concentrations of soluble tumor necrosis factor receptor II (TNFRII) in SM. A subset of TNFRII<superscript>+</superscript> Treg cells with high expression of Foxp3 was increased in severe relative to uncomplicated malaria. In vitro, P. falciparum-infected red blood cells dose dependently induced TNFRII<superscript>+</superscript>Foxp3<superscript>hi</superscript> Treg cells in PBMC from malaria-unexposed donors which showed greater suppressive activity than TNFRII<superscript>-</superscript> Treg cells. The selective enrichment of the Treg cell compartment for a maximally suppressive TNFRII<superscript>+</superscript>Foxp3<superscript>hi</superscript> Treg subset in severe malaria provides a potential link between immune suppression, increased parasite biomass, and malaria disease severity. The findings caution against the induction of TNFRII<superscript>+</superscript>Foxp3<superscript>hi</superscript> Treg cells when developing effective malaria vaccines. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15537366
- Volume :
- 5
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 45437913
- Full Text :
- https://doi.org/10.1371/journal.ppat.1000402