Regulatory T cells in malaria--friend or foe?

Malaria Programme, MRC Laboratories, Fajara, PO Box 273 Banjul, The Gambia.
Trends in Immunology (Impact Factor: 12.03). 02/2010; 31(2):63-70. DOI: 10.1016/
Source: PubMed

ABSTRACT T cell-mediated inflammatory immune responses contribute to both the clearance and pathology of malaria infections; the host's ability to down-regulate inflammation once parasitemia is controlled is crucial to avoid immune-mediated pathology but remains poorly understood. Various regulatory populations of T lymphocytes can modulate inflammatory immune responses and there has been considerable recent interest in the potential for regulatory T cells to modify the outcome of both murine and human malaria infections. Here, we review these studies, focussing in particular on recent studies in humans, propose a model by which different regulatory T cell populations might contribute to the control of inflammation at different stages of infection and discuss the implications for the design of safe and effective malaria vaccines.

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    ABSTRACT: Human diseases caused by protozoan parasites are renowned for their high rates of morbidity and mortality worldwide. Some examples include African trypanosomiasis or sleeping sickness, American trypanosomiasis or Chagas disease, leishmaniases, malaria and babesiosis. These infections tend to follow a chronic rather than an acute course with lifelong persistence of parasites. Regulatory T cells (Treg), in particular the CD4 + CD25 + cell subset, appear to control the immune competence of host response triggered by the presence of parasites, promoting homeostasis and protecting the host from collateral tissue damage whilst allowing parasite persistence. To date, there is still considerable controversy on the characteristics and function of these cells when induced during different protozoan infections, evidencing the need of further research. Therefore, this review aims to provide a comprehensive overview about Treg cells development, phenotype determination and general functions. The above pathologies were used as selected examples to discuss the role of Treg cells during protozoan infections. Understanding of the mechanisms that contribute towards homeostasis and the survival of the host, and simultaneously allow the persistence of the pathogen, may yield important insights for new strategies of prophylaxis and therapy.
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    ABSTRACT: Background. Malaria still infects many Malawian children, and it is a cause of death in some of them. Regulatory T cells (Tregs) help in negating immune-related pathology, it but can also favor multiplication of malaria parasites. The question remains whether children recovering from uncomplicated malaria (UCM) have higher Tregs and interleukin (IL)-10 levels in convalescence. Methods. We recruited children between the ages of 6 and 60 months presenting with acute UCM in Blantyre (low transmission area) and Chikwawa (high transmission area). We observed the children after 1 month and 3 months and analyzed their blood samples for parasitemia, lymphocyte subsets, and levels of the cytokines interferon (IFN)-γ, IL-10, and transforming growth factor (TGF)-β. Blood samples from age-matched controls were also analyzed for the same parameters. Results. Compared with controls, acute UCM was associated with mild lymphopenia, splenomegaly, and high levels of IFN-γ, tumor necrosis factor-α, and IL-10, which normalized in convalescence. In Chikwawa, Treg counts were significantly (P < .0001) higher in convalescence compared with acute disease, whereas in Blantyre, these were as low as in healthy controls both during acute disease and in convalescence. Blantyre had a higher percentage of parasiteamic children (15% versus 12%) in convalescence compared with Chikwawa, but none of these developed symptomatic malaria during the study duration. Concentrations of TGF-β were higher at time points for the study participants and in controls from Blantyre compared with those recruited in Chikwawa. Conclusions. The high transmission area was associated with high Tregs counts and IL-10 concentrations in convalescence, which could have an effect on parasite clearance. We recommend that children recovering from UCM, especially those from high transmission area, should sleep under insecticide-treated nets, be screened for parasitemia, and a provision of antimalarial prophylaxis should be considered.
    01/2015; DOI:10.1093/jpids/piu140