Abstract
BackgroundNaturally acquired immunity to malaria may be lost with lack of exposure. Recent heterogeneous reductions in transmission in parts of Africa mean that large populations of previously protected people may lose their immunity while remaining at risk of infection.MethodsUsing two ethnically similar long-term cohorts of children with historically similar levels of exposure to Plasmodium falciparum who now experience very different levels of exposure, we assessed the effect of decreased parasite exposure on antimalarial immunity. Peripheral blood mononuclear cells (PBMCs) from children in each cohort were stimulated with P. falciparum and their P. falciparum-specific proliferative and cytokine responses were compared.ResultsWe demonstrate that, while P. falciparum-specific CD4+ T cells are maintained in the absence of exposure, the proliferative capacity of these cells is altered considerably. P. falciparum-specific CD4+ T cells isolated from children previously exposed, but now living in an area of minimal exposure (“historically exposed”) proliferate significantly more upon stimulation than cells isolated from children continually exposed to the parasite. Similarly, PBMCs from historically exposed children expressed higher levels of pro-inflammatory cytokines and lower levels of anti-inflammatory cytokines after stimulation with P. falciparum. Notably, we found a significant positive association between duration since last febrile episode and P. falciparum-specific CD4+ T cell proliferation, with more recent febrile episodes associated with lower proliferation.ConclusionConsidered in the context of existing knowledge, these data suggest a model explaining how immunity is lost in absence of continuing exposure to P. falciparum.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0683-6) contains supplementary material, which is available to authorized users.
Highlights
Acquired immunity to malaria may be lost with lack of exposure
We demonstrate that lack of continuing exposure in the historically exposed cohort resulted in increased levels of P. falciparum-specific CD4+ T cell proliferation and pro-inflammatory cytokine production
P. falciparum-specific CD4+ T cells are maintained in the absence of continual exposure To determine whether malaria-specific CD4+ T cells are maintained in the absence of continued exposure, we compared the frequency and function of P. falciparumspecific CD4+ T cell responses between historically and continually exposed children
Summary
Acquired immunity to malaria may be lost with lack of exposure. Recent heterogeneous reductions in transmission in parts of Africa mean that large populations of previously protected people may lose their immunity while remaining at risk of infection. The mechanisms that underpin naturally acquired immunity to malaria (NAI) remain poorly understood, a review of literature suggests that it is comprised of two main components, namely (1) an Bediako et al BMC Medicine (2016) 14:143 anti-parasite component resulting in control of parasite replication and parasite clearance [5, 6] and (2) the ability to tolerate parasites asymptomatically. The latter component is likely to include an immunoregulatory (immune tolerance) element that contributes to control of symptoms and clinical immunity [7, 8]. Continual exposure to P. falciparum appears to result in modulation of inflammation and associated immunopathology through regulation at multiple levels of the immune system
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