Interaction between environment, nutrient-derived metabolites and immunity: A possible role in malaria susceptibility/resistance in Fulani and Dogon of Mali

• Published in: PloS one Vol. 12; no. 12; p. e0189724
• Main Authors: Traore, Karim, Thera, Mahamadou A, Bienvenu, Anne-Lise, Arama, Charles, Bonnot, Guillaume, Lavoignat, Adeline, Doumbo, Ogobara K, Picot, Stephane
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.12.2017; Public Library of Science (PLoS)
• Subjects: Adaptive immunity; Adolescent; Adult; Advanced glycosylation end products; Age; Aged; Aged, 80 and over; Analysis; Bacteria; Bacterial infections; Biology and Life Sciences; Child; Child, Preschool; Chronic exposure; Clonal deletion; Diabetes; Diabetic retinopathy; Diet; Disease Susceptibility; Enzyme-Linked Immunosorbent Assay; Exposure; Female; Food production; Gene polymorphism; Genetic aspects; Genetic polymorphisms; Glycation End Products, Advanced - blood; Glycosylation; Health aspects; Humans; Immune response; Immune system; Immunity; Lipids; Malaria; Malaria - epidemiology; Malaria - immunology; Malaria - parasitology; Male; Mali - epidemiology; Medicine and Health Sciences; Metabolites; Middle Aged; Nucleic acids; Nutrients; Oxidative stress; People and Places; Plasma levels; Plasmodium - classification; Polymorphism; Polymorphism, Genetic; Proteins; Receptors; Research and Analysis Methods; Reverse Transcriptase Polymerase Chain Reaction; Risk factors; Studies; Sugar; Sympatric populations; Training; Vector-borne diseases; Young Adult; Mali
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0189724

The role of some nutrient-derived metabolites on the innate and adaptive immune responses is now established. Global research approach investigating the interplay between environment, lifestyle and the host's immune responses is crucial in the understanding of malaria susceptibility. Advanced Glycation end products (AGE), which are food-derived metabolites result from the link between reducing sugar and amino group of proteins, lipids or nucleic acids. The level of exposure to AGEs varies depending on the type of diet. The dysfunction of the immune system induced by AGE and the cellular receptors for AGEs (RAGE) in susceptibility to bacterial infection has been described. But no study has yet explored their role in susceptibility to malaria. Therefore, we aimed to evaluate systemic AGE and RAGE gene polymorphism in two sympatric populations with previously described difference of susceptibility to malaria. We measured by ELISA the plasma levels of AGEs, and their soluble receptors (sRAGE) from 170 volunteers (68 Fulani and 102 Dogon). We also determined by real-time quantitative PCR the expression of RAGE, and the -374 T/A, -429 T/C polymorphisms and 63 bp deletion by fragment length restriction polymorphism. The prevalence rate of Plasmodium in Fulani and Dogon were respectively 42.64% and 51.30% for P. falciparum, 5.88% and 6.5% for P. malariae, 0% and 2.6% for P. ovale. The average AGE was 12.65 μg/ml, and 496.48pg/ml for sRAGE. Highest levels of sRAGE were observed in Fulani (563,07pg/ml, 95% CI [547.81-580.13] vs 465.68pg/ml, 95% CI [331.19-467.51]) for Dogon, p = 0.00001. Fulani had the lowest mean of AGE (10.21μg/ml, 95% CI [8.02-10.92]) compared to Dogon (16.88μg/ml, 95% CI [13.92-17.96]; p = 0.00001. RAGE was more expressed in Dogon than Fulani (0.08 vs 0.04), P = 0.08. The -374A polymorphism vas more frequent in Fulani (32%) compared to Dogon (20%). The chronic exposure to dietary AGE could lead to immune responses impairment and polymorphism with implications in malaria susceptibility. More studies are necessary to better investigate this hypothesis.