ABSTRACT
Introduction: The proteolytic activity of A Disintegrin and Metalloproteinase 17 (ADAM17) regulates the release of tumor necrosis factor (TNF) and TNF receptors (TNFRs) from cell surfaces. These molecules play important roles in tuberculosis (TB) shaping innate immune reactions and granuloma formation. Methods: Here, we investigated whether single nucleotide polymorphisms (SNPs) of ADAM17 influence TNF and TNFRs levels in 224 patients with active TB (ATB) and 118 healthy close contacts. Also, we looked for significant associations between SNPs of ADAM17 and ATB status. TNF, TNFR1, and TNFR2 levels were measured in plasma samples by ELISA. Four SNPs of ADAM17 (rs12692386, rs1524668, rs11684747, and rs55790676) were analyzed in DNA isolated from peripheral blood leucocytes. The association between ATB status, genotype, and cytokines was analyzed by multiple regression models. Results: Our results showed a higher frequency of rs11684747 and rs55790676 in close contacts than ATB patients. Coincidentally, heterozygous to these SNPs of ADAM17 showed higher plasma levels of TNF compared to homozygous to their respective ancestral alleles. Strikingly, the levels of TNF and TNFRs distinguished participant groups, with ATB patients displaying lower TNF and higher TNFR1/TNFR2 levels compared to their close contacts. Conclusion: These findings suggest a role for SNPs of ADAM17 in genetic susceptibility to ATB.
ABSTRACT
The role of the microbiome in asthma is highlighted, considering its influence on immune responses and its connection to alterations in asthmatic patients. In this context, we review the variables influencing asthma phenotypes from a microbiome perspective and provide insights into the microbiome's role in asthma pathogenesis. Previous cohort studies in patients with asthma have shown that the presence of genera such as Bifidobacterium, Lactobacillus, Faecalibacterium, and Bacteroides in the gut microbiome has been associated with protection against the disease. While, the presence of other genera such as Haemophilus, Streptococcus, Staphylococcus, and Moraxella in the respiratory microbiome has been implicated in asthma pathogenesis, indicating a potential link between microbial dysbiosis and the development of asthma. Furthermore, respiratory infections have been demonstrated to impact the composition of the upper respiratory tract microbiota, increasing susceptibility to bacterial diseases and potentially triggering asthma exacerbations. By understanding the interplay between the microbiome and asthma, valuable insights into disease mechanisms can be gained, potentially leading to the development of novel therapeutic approaches.
