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Background  Toll-like receptors play a key role in innate immunity by recognizing pathogens and activating appropriate responses. Pathogens express several signal molecules (pathogen-associated molecular patterns, PAMPs) essential for survival and pathogenicity. Recognition of PAMPs triggers an array of anti-microbial immune responses through the induction of various inflammatory cytokines. The objective of this work was to perform a case-control study to characterize the distribution of polymorphisms in three candidate genes ( toll-like receptor  2,  toll-like receptor  4,  toll-like receptor  9) and to test their role as potential risk factors for tuberculosis infection in water buffalo ( Bubalus bubalis ).    Results  The case-control study included 184 subjects, 59 of which resulted positive to both intradermal TB test and  Mycobacterium bovis  isolation (cases) and 125 resulted negative to at least three consecutive intradermal TB tests. The statistical analysis indicated that two polymorphisms exhibited significant differences in allelic frequencies between cases and controls. Indeed, the TT genotype at  TLR9  2340 C > T locus resulted significantly associated with susceptibility to bovine tuberculosis ( P  = 0.030, OR = 3.31, 95% CI = 1.05-10.40). One polymorphism resulted significantly associated with resistance to the disease, and included the CC genotype, at the  TLR4  672 A > C locus ( P  = 0.01, OR = 0.26, 95% CI = 0.08-0.80). Haplotype reconstruction of the  TLR2  gene revealed one haplotype (CTTACCAGCGGCCAGTCCC) associated with disease resistance ( P =  0.04, OR = 0.51, 95% CI = 0.27–0.96), including the allelic variant associated with disease resistance.    Conclusions  The work describes novel mutations in bubaline  TLR2 ,  TLR4  and  TLR9  genes and presents their association with  M. bovis  infection. These results will enhance our ability to determine the risk of developing the disease by improving the knowledge of the immune mechanisms involved in host response to mycobacterial infection, and will allow the creation of multiple layers of disease resistance in herds by selective breeding.

bmc genomic data

Identification of single nucleotide polymorphisms in Toll-like receptor candidate genes associated with tuberculosis infection in water buffalo (Bubalus bubalis)