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Parasite-dependent expansion of TNF receptor II-positive regulatory T cells with enhanced suppressive activity in adults with severe malaria

Minigo, Gabriela, Woodberry, Tonia, Piera, Kim A., Salwati, Ervi, Tjitra, Emiliana, Kenangalem, Enny, Price, Ric N., Engwerda, Christian R., Anstey, Nicholas M. and Plebanski, Magdalena (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):1-10.

Document type: Journal Article
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IRMA ID 10728xPUB10
Title Parasite-dependent expansion of TNF receptor II-positive regulatory T cells with enhanced suppressive activity in adults with severe malaria
Author Minigo, Gabriela
Woodberry, Tonia
Piera, Kim A.
Salwati, Ervi
Tjitra, Emiliana
Kenangalem, Enny
Price, Ric N.
Engwerda, Christian R.
Anstey, Nicholas M.
Plebanski, Magdalena
Journal Name PLoS Pathogens
Publication Date 2009
Volume Number 5
Issue Number 4
ISSN 1553-7374   (check CDU catalogue  open catalogue search in new window)
Start Page 1
End Page 10
Total Pages 10
Place of Publication San Francisco, CA, United States
Publisher Public Library of Science
HERDC Category C1 - Journal Article (DEST)
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.
Keywords Plasmodium falciparum
severe malaria
Treg cells
Indonesia
DOI http://dx.doi.org/10.1371/journal.ppat.1000402   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)


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