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. 2024 Mar 4;24(1):275.
doi: 10.1186/s12879-024-09149-8.

An elevated level of interleukin-17A in a Senegalese malaria cohort is associated with rs8193038 IL-17A genetic variant

Fatou Thiam  1 , Gora Diop  2   3 , Cedric Coulonges  4 , Celine Derbois  5 , Alassane Thiam  3 , Abou Abdallah Malick Diouara  6 , Mame Ndew Mbaye  6 , Mamadou Diop  6 , Cheikh Momar Nguer  6 , Yakhya Dieye  6   7 , Babacar Mbengue  8 , Jean-Francois Zagury  4 , Jean-Francois Deleuze  5 , Alioune Dieye  8
Affiliations

An elevated level of interleukin-17A in a Senegalese malaria cohort is associated with rs8193038 IL-17A genetic variant

Fatou Thiam et al. BMC Infect Dis. .

Abstract

Malaria infection is a multifactorial disease partly modulated by host immuno-genetic factors. Recent evidence has demonstrated the importance of Interleukin-17 family proinflammatory cytokines and their genetic variants in host immunity. However, limited knowledge exists about their role in parasitic infections such as malaria. We aimed to investigate IL-17A serum levels in patients with severe and uncomplicated malaria and gene polymorphism's influence on the IL-17A serum levels. In this research, 125 severe (SM) and uncomplicated (UM) malaria patients and 48 free malaria controls were enrolled. IL-17A serum levels were measured with ELISA. PCR and DNA sequencing were used to assess host genetic polymorphisms in IL-17A. We performed a multivariate regression to estimate the impact of human IL-17A variants on IL-17A serum levels and malaria outcomes. Elevated serum IL-17A levels accompanied by increased parasitemia were found in SM patients compared to UM and controls (P < 0.0001). Also, the IL-17A levels were lower in SM patients who were deceased than in those who survived. In addition, the minor allele frequencies (MAF) of two IL-17A polymorphisms (rs3819024 and rs3748067) were more prevalent in SM patients than UM patients, indicating an essential role in SM. Interestingly, the heterozygous rs8193038 AG genotype was significantly associated with higher levels of IL-17A than the homozygous wild type (AA). According to our results, it can be concluded that the IL-17A gene rs8193038 polymorphism significantly affects IL-17A gene expression. Our results fill a gap in the implication of IL-17A gene polymorphisms on the cytokine level in a malaria cohort. IL-17A gene polymorphisms also may influence cytokine production in response to Plasmodium infections and may contribute to the hyperinflammatory responses during severe malaria outcomes.

Keywords: Plasmodium falciparum; Cytokines; Severe malaria; Single nucleotide polymorphism.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Parasite density and IL17A levels in different categories of enrolled subjects. a, b Serum level IL-17 between SM, UM and Control group and survivors and deceased SM patients. c, d Parasitemia between SM, UM and Control group, survivors, and deceased SM patients. Data representing mean pg/ml ± SE for IL17A and mean P/uL for parasitemia were analysed with one way ANOVA or Student Test for comparison. P < 0.05 was considered statistically significant
Fig. 2
Fig. 2
Mapping of Interleukin -17A (IL-17A) gene and the polymorphisms genotyped. Schema of the gene encoding Interleukin 17 A (IL17A) (a) The human IL17A gene (located at 6p12-2) contains 3 exons that span 4 kb. Exons are described by number. AUG: the transcription start site. Black arrows mark eight specific polymorphisms identified in the IL-17A gene
Fig. 3
Fig. 3
Concentration of IL-17A according to its genotypes. ELISA quantified serum levels of IL-17A in a total of 173 subjects comprising Severe and Uncomplicated malaria subjects and Controls. Mean IL-17A levels in the different genotypes of rs2275913 (a) rs3819024 (b) rs2275913 (c) rs81933037 (d) rs3819025 (e) rs8193038 (f) rs17880588 (g) rs3748067 (h) Polymorphisms were compared by ANOVA followed by Tukey’s post-test. No significant association between IL-23A (rs11171806) and levels of IL-23 was observed (b). A p-value of less than 0.05 was taken as significant
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