Polymorphisms in SIGLEC1 contribute to susceptibility to pulmonary active tuberculosis possibly through the modulation of IL-1ß.

Siglec-1/CD169 is a sialoadhesin expressed by macrophages thought to function in cell-to-cell interactions. In the lung, the expression of Siglec-1 is specific for alveolar macrophages and single nucleotide polymorphisms (SNPs) in SIGLEC1 have been recently associated with asthma severity. Taking in account the role of alveolar macrophages in the control of M. tuberculosis and the poor literature about the contribution of SIGLEC1 genetics in M. tuberculosis susceptibility and development of pulmonary active TB, selected SNPs in SIGLEC1 were analysed in a case/control cohort from a TB endemic area of Brazil Amazon. Our findings evidenced for the first time the novel association between SIGLEC1 rs3859664 SNP and active pulmonary TB. Intriguingly, carriers of the polymorphism produced less IL-1ß than non-carriers, suggesting the possible involvement of Siglec-1 signalling pathway with inflammasome complex.