TLR2 Polymorphisms Modeling and Italian Mediterranean Water Buffalo Brucellosis.

Brucellosis represents a serious economic problem for the livestock industry. It causes late term abortion, decreased milk production, and animal culling. In Italy, brucellosis is mainly spread in the area of Caserta (Campania region), where 43% of the Italian Mediterranean water buffalo population is concentrated. Different studies have demonstrated that TLR2 recognizes the Brucella abortus surface lipoproteins and activates the immune response by heterodimerization with TLR1 or TLR6. This study investigates whether the SNPs on TLR2 could compromise protein functionality, thus influencing the susceptibility of the Italian Mediterranean water buffaloes to brucellosis. A total of 194 water buffaloes from the province of Caserta were grouped as positive and negative for B. abortus. The TLR2 sequencing was carried out for the identification of SNPs; the computational investigation was for assessing the SNPs effects on protein activity, and the genotyping analysis was performed for verifying the in silico results. Results from the TLR2 sequencing and computational analyses (Docking, MDS, APBS) evidenced that two amino acid substitutions, A125V and S345N, were able to compromise the TLR2 structure and its heterodimerization process, thus influencing the immune response. The genotyping analysis revealed that Valina at 125 was correlated with resistance to brucellosis (OR = 0.22; p-value = 0.015), and Serine at 345 was protective against B. abortus infection (OR = 0.50; p-value = 0.049). These results provide preliminary evidence of the association between amino acid substitutions and resistance to brucellosis in the Mediterranean water buffalo, contributing to animal management and welfare.