Abstract
Circulation CD4+CD25+FoxP3+ regulatory T cells (Tregs) have been associated with the delicate balancing between control of overwhelming acute malaria infection and prevention of immune pathology due to disproportionate inflammatory responses to erythrocytic stage of the parasite. While the role of Tregs has been well-documented in murine models and P. falciparum infection, the phenotype and function of Tregs in P. vivax infection is still poorly characterized. In the current study, we demonstrated that patients with acute P. vivax infection presented a significant augmentation of circulating Tregs producing anti-inflammatory (IL-10 and TGF-β) as well as pro-inflammatory (IFN-γ, IL-17) cytokines, which was further positively correlated with parasite burden. Surface expression of GITR molecule and intracellular expression of CTLA-4 were significantly upregulated in Tregs from infected donors, presenting also a positive association between either absolute numbers of CD4+CD25+FoxP3+GITR+ or CD4+CD25+FoxP3+CTLA-4+ and parasite load. Finally, we demonstrate a suppressive effect of Treg cells in specific T cell proliferative responses of P. vivax infected subjects after antigen stimulation with Pv-AMA-1. Our findings indicate that malaria vivax infection lead to an increased number of activated Treg cells that are highly associated with parasite load, which probably exert an important contribution to the modulation of immune responses during P. vivax infection.
Highlights
Malaria is a major worldwide scourge, infecting and killing several millions of individuals each year [1]
No difference in the absolute number of this lymphocyte population was observed between malaria infected and naıve individuals
Consistent evidence based on experimental models and human P. falciparum infection suggest that Tregs may contribute to the onset of infection, the role of these cells during malaria and the possible mechanisms of regulation are not yet fully elucidated
Summary
Malaria is a major worldwide scourge, infecting and killing several millions of individuals each year [1]. The worldwide burden of P. vivax malaria has not been reliably estimated, the annual infections may range from 132 million to 391 million people [4] and 2.6 billion people living in areas of risk [5]. This disease affects poor people living in least developed and developing countries. Infection by this parasite may result in life-long learning impairment, incapacitating adults for work, with major direct economic consequences due to loss of productivity and depletion of the already meager financial resources [6]. Despite the importance of this disease, representing the most prevalent recurrent malaria [7], the immunological mechanisms associated to the control of parasite levels and disease severity are not fully understood
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