Parasites increase their survival rate in the host by means of a complex interaction with the host immune system. However understanding such interaction on the part of the host and parasite during infections still remains a fundamental issue. In such processes, it is believed that the host regulatory T (Tregs) cells play an essential role [
1,
2]. The parasite induces a regulatory T cell (Tregs) population that can modulate the magnitude of effector T cell functions thereby leading to a subtle immune response during infections [
3]. The regulatory T cell populations remain diverse; a few of them are induced during infections while the others are considered to be natural Tregs vitally implicated in averting autoimmunity [
4]. Tregs are believed to influence host inflammatory and immune responses via mechanisms of cell-to-cell contact, inhibitory cytokines and cytokine deprivation [
3]. Pathogen driven selection operating on the host immune genes can impose a nucleotide variation in the primed sequence whereby substantial changes in gene expression is directed [
2]. Human gene expression is a controlled transcriptional process in the promoter region of a given gene and is regulated by
cis-acting DNA sequence elements. Any nucleotide alteration in the promoter region is likely to alter the gene expression, reflecting the level of susceptibility to a parasitic infection as well as Treg expression [
5]. A number of loci are known to be associated with Treg activity. Genes such as
IL10, IL13, STAT6, TNFRSF18, TLRs and
FOXP3 have been as key players in regulating Tregs [
2,
4‐
7]. One such gene of interest is the interleukin 2 (
IL2) and its receptor
IL2R alpha (
CD25) that are known to modulate the proliferation and differentiation of T cells and are essential for peripheral homeostasis of the CD4
+CD25
+ Tregs [
8].
The human
IL2 is located on the q arm of the chromosome 4 (specifically 4q27) and its receptor
IL2R alpha (
CD25) maps to the p arm of the chromosome 10 (specifically 10p15.1). The human IL-2 is primarily produced by T cells in response to antigenic stimulation and is a major mediator of the immune response [
9]. Studies have demonstrated that IL-2 is essential for the proliferation and maintenance of Tregs and can disrupt Treg homeostasis [
10,
11], whereas the IL-2R plays a significant role in Treg differentiation and proliferation [
12]. Tregs have been shown to constitutively express IL-2R (CD25), allowing Tregs to respond to low levels of IL-2 produced by conventional CD4+ T cells [
10,
11]. The removal of IL-2 from activated T cells can lead to a deprivation of cells, which is indicated by studies on
IL2-deficient mice [
13]. The IL-2 receptor has three chains, α, β and γ, which constitute the high affinity
IL2 receptor. The
IL2R alpha (
CD25) is responsible for activating the
IL2 signaling complex and regulates the signal transduction [
14,
15]. The IL2-R alpha subunit forms the largest of the three IL-2/IL2-R interfaces. Association of α chain with the β and γ heterodimer creates a receptor with a much higher affinity for IL-2 than the β and γ chains receptor [
16]. Antigen recognition by the T cell receptor induces the synthesis or activation of the transcription factors such as
NFAT, AP-1, and
NFκB, which are located in the promoter region of the
IL2 gene and are essential for activating its transcription [
17]. Studies have pointed to the single nucleotide polymorphisms (SNPs) located within the upstream −10 kb of the
IL2 gene that includes the promoter region, and possibly even beyond, thereby contributing to
IL2 transcriptional properties
in vivo[
18]. The inhibition of
IL2R alpha (
CD25) during thymocyte differentiation is related to
IL2R alpha promoter after response to pre-TCR signals and is essential for the specific response of mature T cells later on [
19]. Additionally studies have shown that SNPs within
IL2R alpha are associated with both Grave’s disease and Type1 diabetes [
20,
21]. Reports have indicated that polymorphisms in the genes encoding
IL2 are associated with ulcerative colitis, inflammatory bowel disorder, rheumatoid arthritis and Behcet’s disease [
22‐
25], whereas the receptor of
IL2, the
IL2R alpha variants were associated with type I diabetes and multiple sclerosis [
21,
26,
27].
In the current study, our goal is to identify regulatory single nucleotide polymorphisms (SNPs) in the promoter region of the IL2 and its receptor IL2R alpha (CD25) gene loci in a Sub-Saharan African population exposed to a wide array of parasitic diseases. In this study, with a view to identifying regulatory SNPs in the promoter regions of the IL2 and its receptor IL2R alpha (CD25), we sequenced the promoter region of such genes as were upstream of the transcriptional start site, using samples from 40 unrelated Gabonese individuals. The identified regulatory SNPs were further validated for their allelic gene expression, which may possibly be correlated with various physiological responses.