Parasite-Dependent Expansion of TNF Receptor II–Positive Regulatory T Cells with Enhanced Suppressive Activity in Adults with Severe Malaria

Gabriela Minigo, Tonia Woodberry, Kim A. Piera, Ervi Salwati, Emiliana Tjitra, Enny Kenangalem, Ric N. Price, Christian R. Engwerda, Nicholas M. Anstey and Magdalena Plebanski (2009) Parasite-Dependent Expansion of TNF Receptor II–Positive Regulatory T Cells with Enhanced Suppressive Activity in Adults with Severe Malaria. PLoS Pathogens, 5 4: e1000402.1-e1000402.10. doi:10.1371/journal.ppat.1000402


Author Gabriela Minigo
Tonia Woodberry
Kim A. Piera
Ervi Salwati
Emiliana Tjitra
Enny Kenangalem
Ric N. Price
Christian R. Engwerda
Nicholas M. Anstey
Magdalena Plebanski
Title Parasite-Dependent Expansion of TNF Receptor II–Positive Regulatory T Cells with Enhanced Suppressive Activity in Adults with Severe Malaria
Formatted title
Parasite-Dependent Expansion of TNF Receptor II–Positive Regulatory T Cells with Enhanced Suppressive Activity in Adults with Severe Malaria
Journal name PLoS Pathogens   Check publisher's open access policy
ISSN 1553-7366
Publication date 2009-04-01
Year available 2009
Sub-type Article (original research)
DOI 10.1371/journal.ppat.1000402
Open Access Status DOI
Volume 5
Issue 4
Start page e1000402.1
End page e1000402.10
Total pages 10
Editor Kasturi Haldar
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2010
Language eng
Formatted abstract
Severe Plasmodium falciparum malaria is a major cause of global mortality, yet the immunological factors underlying progression to severe disease remain unclear. CD4+CD25+ 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+CD25+Foxp3+CD127lo 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+ 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+Foxp3hi Treg cells in PBMC from malaria-unexposed donors which showed greater suppressive activity than TNFRII− Treg cells. The selective enrichment of the Treg cell compartment for a maximally suppressive TNFRII+Foxp3hi 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+Foxp3hi Treg cells when developing effective malaria vaccines.

Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ
Additional Notes Article # e1000402

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Tue, 30 Mar 2010, 23:42:12 EST by Amanda Jones on behalf of Medicine - Royal Brisbane and Women's Hospital