Gene Expression and In Vitro Pharmacogenetic Studies of Dopamine and Serotonin Gene Receptors in Tuberculosis

Background: Dopamine and serotonin receptors are present in lymphocytes, macrophages, and neutrophils, and have a mediating role in the immune system to respond to infections, including bacterial tuberculosis.

Materials and methods: In this study, at first, the changes in the expression pattern of 5 dopamine and 2 serotonin (5HTR2B & 5HTR2C) gene receptors were examined in the two groups of healthy and Tuberculosis patients using Real-Time PCR. Then pharmacogenetic studies aimed to induce autophagy on a lung monocyte cell line (THP1) infected with the standard strain of Mycobacterium tuberculosis (H37RV) were performed. Stimulation of the pro-inflammatory pathway by secreting cytokines before and after drug efficacy was investigated.

Results: According to the result, dopamine receptor 2 genes showed decreased expression in patients with tuberculosis compared to normal individuals, and serotonin receptor genes showed increased expression. Additionally, with the effects of Bromocriptine and Fluoxetine, pro-inflammatory pathways were activated in macrophages infected with H37RV, and ELISA results showed that the levels of IL6 and TNFα secreted in these cells were significantly increased.

Conclusion: According to the results, these receptors agonists or antagonists can activate the autophagy pathway to kill TB bacteria.