Cytokine Profiling in Immigrants with Clinical Malaria after Extended Periods of Interrupted Exposure to Plasmodium falciparum

Abstract

Immunity to malaria is believed to wane with time in the absence of exposure to Plasmodium falciparum infection, but immunoepidemiological data on longevity of immunity remain controversial. We quantified serum cytokines and chemokines by suspension array technology as potential biomarkers for durability of immunity in immigrants with clinical malaria after years without parasite exposure. These were compared to serum/plasma profiles in naïve adults (travelers) and semi-immune adults under continuous exposure, with malaria, along with immigrant and traveler patients without malaria. Immigrants had higher levels of IL-2, IL-5 and IL-8 compared to semi-immune adults with malaria (P≤0.0200). Time since immigration correlated with increased IL-2 (rho=0.2738P=0.0495) and IFN-γ (rho=0.3044P=0.0282). However, immigrants did not show as high IFN-γ concentrations as travelers during a first malaria episode (P<0.0001). Immigrants and travelers with malaria had higher levels of IFN-γ, IL-6, and IL-10 (P<0.0100) than patients with other diseases, and IL-8 and IL-1β were elevated in immigrants with malaria (P<0.0500). Therefore, malaria patients had a characteristic strong pro-inflammatory/Th1 signature. Upon loss of exposure, control of pro-inflammatory responses and tolerance to P. falciparum appeared to be reduced. Understanding the mechanisms to maintain non-pathogenic effector responses is important to develop new malaria control strategies.

Changes in immunological profile as a function of urbanization and lifestyle

“…The finding that urban Senegalese display a lower pro‐inflammatory profile compared with rural subjects suggests that immunological changes might be associated with a break from traditional lifestyle and lower exposure to infections. This is supported by the reports of changes in immunological profiles of African migrants in Europe after several years . More recently, Smolen et al .…”

“…This is supported by the reports of changes in immunological profiles of African migrants in Europe after several years. 37,38 More recently, Smolen et al 39 have shown, in 2-year-old infants, that cytokine and chemokine production in response to pattern recognition receptor ligands were lower in South African infants compared with Europeans, North Americans and South American infants. In terms of immune responsiveness between low (in Africa) and high (in Europe) income countries, our results are different as we report, if any, a higher immunological response in Senegalese.…”

High Antibody Responses against Plasmodium falciparum in Immigrants after Extended Periods of Interrupted Exposure to Malaria

“…falciparum may be reduced [62]. No correlation was found between plasma cytokine or chemokine concentrations and Ab levels.…”

Evaluating antidisease immunity to malaria and implications for vaccine design

“…Although several environmental factors as well as patient autonomous factors, including age and genetics, might influence these observations, these findings are suggestive of processes that lead to reduced inflammation at high exposure levels. Similarly, semi‐immune adults who continually reside (continuous exposure) in an endemic area had lower levels of Th1 cytokines relative to levels observed in travellers experiencing their first clinical episode of malaria, and in immigrants visiting an endemic area after a long period without exposure 104. A controlled human model of malaria infection also observed higher natural killer cells, natural killer γδ T cells, and CD4 + IFN‐ γ responses in naive Dutch subjects compared with observed levels in exposed Tanzanian adults from an endemic region,105 suggesting a control of inflammatory response with increased history of exposure.…”