Immune activation and induction of memory: lessons learned from controlled human malaria infection with Plasmodium falciparum

Abstract

Controlled human malaria infections (CHMIs) are a powerful tool to assess the efficacy of drugs and/or vaccine candidates, but also to study anti-malarial immune responses at well-defined time points after infection. In this review, we discuss the insights that CHMI trials have provided into early immune activation and regulation during acute infection, and the capacity to induce and maintain immunological memory. Importantly, these studies show that a single infection is sufficient to induce long-lasting parasite-specific T- and B-cell memory responses, and suggest that blood-stage induced regulatory responses can limit inflammation both in ongoing and potentially future infections. As future perspective of investigation in CHMIs, we discuss the role of innate cell subsets, the interplay between innate and adaptive immune activation and the potential modulation of these responses after natural pre-exposure.

Early Immune Regulatory Changes in a Primary Controlled Human Plasmodium vivax Infection: CD1c + Myeloid Dendritic Cell Maturation Arrest, Induction of the Kynurenine Pathway, and Regulatory T Cell Activation

“…One possible explanation for impaired immunity is modulation of immune regulatory pathways by Plasmodium. Experimentally induced human Plasmodium infection, also referred to as controlled human malaria infection (CHMI), provides a unique opportunity to gain insights into the shaping of primary immune and regulatory responses in malaria-naive volunteers (6).…”

Plasmodium Falciparum Infection: In Silico Preliminary Studies

“…From this, they penetrate into the red blood cells and they will continue the biological cycle, establishing blood schizogony, and releasing new merozoites, each cycle within a range of 36 to 48 hours. At this time -when there is the destruction of red blood cells and release of the new agents in the circulation -there are pigments that act as exogenous pyrogen, triggering the immune response and consequent production and release of endogenous pyrogens, the interleukins (REY, 2008;SCHOLZEN;SAUERWEIN, 2016). Thus, there is fever, a characteristic sign of malaria (fever paroxysm).…”

Malaria vaccines and human immune responses

“…In contrast, when the immunized volunteers are challenged with blood-stage parasites, they are not protected, suggesting that this immunity is directed to preerythrocytic stages ([14]. In addition, this controlled human challenge model has enabled investigation of immune activation during infection (recently reviewed in [15]).…”