MicroRNAs (miRNAs) play an important role in diseases development. Therefore, human miRNAs may be able to inhibit the survival of Mycobacterium tuberculosis (Mtb) in the human host by targeting critical genes of the pathogen. Mutations within miRNAs can alter their target selection, thereby preventing them from inhibiting Mtb genes, thus increasing host susceptibility to the disease.
Tuberculosis (TB) is a leading cause of morbidity and mortality in Thailand. Cytokines play important roles in defense against Mycobacterium tuberculosis infection. Interleukin (IL)-4 is one of the anti-inflammatory cytokines and has been found to be elevated in TB patients. The common polymorphisms in IL-4 gene, including IL-4-590C/T, IL-4-33C/T, and IL-4-variable number of tandem repeats (VNTR) intron 3 have been reported to be associated with risk for some diseases. The purpose of this study was to investigate possible associations between the above mentioned three common functional polymorphisms in the IL-4 gene in patients with pulmonary tuberculosis (PTB) in a Thai population. Forty three patients with PTB and 90 healthy control subjects were studied. The three common polymorphisms of the IL-4 gene were determined using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). The allele and genotype frequencies of IL-4 -590 C/T, -33 C/T, VNTR intron 3 polymorphisms did not show significant differences between PTB patients and healthy controls (genotype: p=0.88, p=0.92, p=0.40; allele: p=0.38, p=0.44, p=0.53, respectively). However, the allele distribution of the IL-4 -590 C, -33 C, and VNTR R3 was higher among PTB patients (25.58%, 25.58%, 25.58%, respectively) than among control subjects (20%, 20.48%, 19.44%, respectively). This may suggest that IL-4-590C/T, -33C/T and VNTR intron 3 might play a role in susceptibility to PTB. A larger cohort may possibly help conclude our findings.
The acquired immune response against tuberculosis is commonly associated with T-cell responses with little known about the role of B cells or antibodies. There have been suggestions that B cells and humoral immunity can modulate the immune response to Mycobacterium tuberculosis. However, the mechanisms involving B-cell responses in M. tuberculosis are not fully understood, in particular the antibody gene preferences. We hypothesized that a preferential use of V genes can be seen associated with resistance to infection mainly in the IgA isotype, which is of prominent importance for infection by pathogens via the mucosal route. We studied healthy individuals with long-term exposure to tuberculosis, infected (TST(+) ) and uninfected TST(-) ) with M. tuberculosis. From a total of 22 V genes analysed, the TST(-) population preferred the VH 3-23 and Vκ1 genes. The VH 3-23 genes were subsequently subjected to 454 amplicon sequencing. The TST(-) population showed a higher frequency of the D3-10 segment compared with the D3-22 segment for the TST(+) population. The J segment usage pattern was similar for both populations with J4 segment being used the most. A preferential pairing of J4 segments to D3-3 was seen for the TST(-) population. The antibodyome difference between both populations suggests a preference for antibodies with VH 3-23, D3-3, JH 4 gene usage by the TST(-) population that could be associated with resistance to infection with M. tuberculosis.