Effects of TNF-α and IL-10-819 T>C single nucleotide polymorphisms on urogenital schistosomiasis in preschool children in Zimbabwe

Abstract

Background: Knowledge gaps exist between host genetic factors and susceptibility to schistosomiasis.

Objective: This study determined cytokine levels and single nucleotide polymorphisms of tumour necrosis factor (TNF)-α (rs1800629) and interleukin (IL)-10 (rs1800871) and their possible impact on susceptibility to schistosomiasis in preschool-age children in the Madziva area of Shamva district, Mashonaland Central province, Zimbabwe.

Methods: Urogenital schistosomiasis was diagnosed using the urine filtration method, while a sandwich enzyme-linked immunosorbent assay was used for cytokine level determination. The survey was done in August 2015 and reinfection levels post treatment were assessed at 3, 6 and 12 months. Amplification refractory mutation system polymerase chain reaction with visualisation on 2% agarose gel electrophoresis was used for genotyping.

Results: Schistosomiasis prevalence was found to be 10.5% (59/563). Reinfections were detected in only six children at 3 months and only one was reinfected at 12 months. There were no significant differences in TNF-α-308 G/A allele or genotype frequencies between the Schistosoma haematobium infected participants (p = 0.360) and uninfected participants (p = 0.279). However, no children with the IL-10-819 TT genotype had schistosomiasis. The TNF-α GG genotype corresponded with significantly lower TNF-α levels when compared with the GA or AA genotypes (p < 0.001), and TNF-α levels were significantly lower in infected children compared to uninfected children (p < 0.001).

Conclusion: Higher TNF-α levels and lower IL-10 levels are potentially protective against schistosomiasis infection. The IL-10-819 TT genotype is potentially protective against infection through its association with lower IL-10 levels.

Keywords: Schistosoma haematobium; cytokines; polymorphisms; protective immunity; susceptibility.

FIGURE 1

Genotypes, cytokine levels and infection status in preschool children from Madziwa, Shamva district, Zimbabwe, September 2018. (a) Genotypes and TNF-α production (mean level for AA is 179.3 ± 31.2 pg/mL n = 34, GA is 176.8 ± 23.8 pg/mL n = 98 and GG is 131.6 ± 36 pg/mL n = 14); (b) TNF-α levels against infection intensity (239 ± 71.6 pg/mL n = 23 and 210 ± 17.6 pg/mL n = 286); (c) Genotypes against IL-10 plasma levels (CC – 528.5 pg/mL, CT – 323.8 pg/mL and TT – 309.4 pg/mL) (d) IL-10 plasma levels against infection status (452.5 pg/mL and 376.4 pg/mL).