Regulatory T cells control onset and course of malaria
Malaria is a major global health problem responsible for more than one million deaths annually. Severity of malaria disease is associated with the inability of host immune cells to efficiently eliminate malaria parasites from the blood. Little is known about immune regulatory factors controlling the onset of severe and potentially fatal malaria. Regulatory T (Treg) cells are a small specialized subset of immune cells that suppress the activation and expansion of effector immune cells which partake in parasite elimination. Scientists have now investigated the relationship between Treg cells, parasite burden, and disease severity in adult malaria patients with either uncomplicated or severe malaria.
They were able to demonstrate that Treg cell frequency was elevated in malaria patients and associated with high parasite burden in severe malaria but not in uncomplicated malaria. This type of cell turns off the immune system and can allow the parasite to grow uncontrollably. Comparison of Treg cell characteristics allowed them to identify a new highly suppressive subset of Treg cells that was elevated in severe malaria patients. When comparing Treg cell characteristics, the team was able to identify elevated levels of a new highly suppressive subset of Treg cells in those patients with severe malaria. The regulatory (Treg) cell subset associated with severe disease in humans expresses a unique combination of surface markers, including TNFRII. Regulatory T (Treg) cells are a small specialized subset of immune cells that suppress the activation and expansion of effector immune cells, which partake in parasite elimination.
These results indicate that severe malaria is accompanied by the induction of highly suppressive Treg cells that can promote parasite growth and caution against the induction of these Treg cells when developing effective malaria vaccines. It is estimated that 500 million people live in areas where there is a risk of getting malaria. The severe form of the disease causes death in 1-3 million people each year. Until now it had been largely unknown what bodily factors enable some patients to fight and survive the disease, while other patients contract the severe form of the disease and sometimes die. Targeting this cell type may lead to new drugs and immunotherapeutics against malaria. Further studies are needed to determine if this new cell may also be promoting severe forms of other inflammatory diseases.
Parasite-Dependent Expansion of TNF Receptor II–Positive Regulatory T Cells with Enhanced Suppressive Activity in Adults with Severe Malaria. 2009 PLoS Pathog 5(4): e1000402
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 and severe malaria relative to exposed asymptomatic controls. In patients with SM, Treg cell frequency correlated positively with parasitemia and total parasite biomass, 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 TNFRII2 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.
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Tags: Biology, Health, Immunology, Malaria, Medicine, Microbiology, Plasmodium, Science, Vaccines
