The relationship of IL-10 polymorphisms and brucellosis resistance in Mediterranean water buffalo

Interleukin-10 (IL-10) is one of the key anti-inflammatory cytokines produced during infections to suppress inflammation and to limit host tissue damages. However, some Gram-negative bacteria, like Brucella abortus (B. abortus), use IL-10 for neutralizing the host defensive mechanisms thus surviving within the host cells. Polymorphisms in the IL-10 gene may affect the structure of the resulting protein and consequently its interaction with the proper IL-10 receptor (IL-10R), thus potentially compromising the inflammatory pathway triggered by pathogens such as B. abortus. This study aimed to assess the relationship between IL-10 polymorphisms and brucellosis using a combined methodology: in silico analyses (i.e. docking and Molecular Dynamic Simulations) - for predicting the protein modifications induced by single nucleotide polymorphisms (SNPs) - and association study. The predictive analysis evidenced that the substitution of Threonine at position 175 with Methionine in the IL-10 protein sequence, may affect the IL-10/IL-10R interaction, while the genotyping analysis revealed that the g.4002T allele - resulting in the T175M substitution - is associated with resistance to brucellosis (OR = 0.45; p-value = 0.015), thus supporting the computational predictions. This study suggests that the identified genetic variant alters the IL-10 structure and its interaction with the receptor, which may contribute to increase resistance to brucellosis, ultimately favouring pathogen clearance. The proposed approach could represent an alternative strategy for livestock disease management and control.