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

BMC Genetics

Giorgio Galiero⁴  Pier Luigi Acutis²  Paolo Pasquali³  Amalia Barone¹  Michela Tarantino³  Rosanna Desiato²  Maria Grazia Maniaci²  Giovanna Urciuolo⁴  Giorgia Borriello⁴  Maria Gabriella Lucibelli⁴  Simone Peletto²  Flora Alfano⁴ 

[1] Dipartimento di Agraria, Università degli Studi di Napoli “Federico II”, Via Università 100, Portici, 80055, Italy;Istituto Zooprofilattico Sperimentale del Piemonte Liguria e Valle d’Aosta, Via Bologna, 148, Torino, 10154, Italy;Istituto Superiore di Sanità, Dipartimento di Sanità Pubblica Veterinaria e Sicurezza Alimentare, Viale Regina Elena, 299, Roma, 00161, Italy;Istituto Zooprofilattico Sperimentale del Mezzogiorno, Via Salute, 2, Portici, Italy

关键词: Case–control study;    Genetic resistance;    TLRs;    Bubalus bubalis;   

Others  :  1085048
DOI  :  10.1186/s12863-014-0139-y

 received in 2014-03-12, accepted in 2014-11-27,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Alfano et al.; licensee BioMed Central.

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