Human genes in TB infection: their role in immune response

Abstract

Tuberculosis (TB) caused by the human pathogen Mycobacterium tuberculosis, is the leading cause of morbidity and mortality caused by infectious agents worldwide. Recently, there has been an ongoing concern about the clarification of the role of specific human genes and their polymorphisms involved in TB infection. In the vast majority of individuals, innate immune pathways and T-helper 1 (Th1) cell mediated immunity are activated resulting in the lysis of the bacterium. Firstly, PTPN22 R620W polymorphism is involved in the response to cases of infection. The Arg753Gln polymorphism in TLR-2 leads to a weaker response against the M. tuberculosis. The gene of the vitamin D receptor (VDR) has a few polymorphisms (BsmI, ApaI, Taq1, FokI) whose mixed genotypes alter the immune response. Solute carrier family 11 member (SLC11A1) is a proton/divalent cation antiporter that is more familiar by its former name NRAMP1 (natural resistance associated macrophage protein 1) and can affect M. tuberculosis growth. Polymorphisms of cytokines such as IL-10, IL-6, IFN-g, TNF-a, TGF-b1 can affect the immune response in various ways. Finally, a major role is played by M. tuberculosis antigens and the Ras-associated small GTP-ase 33A. As far as we know this is the first review that collates all these polymorphisms in order to give a comprehensive image of the field, which is currently evolving.

Evaluation of tumor necrosis factor (TNF)-α mRNA expression level and the rs1799964 polymorphism of the TNF-α gene in peripheral mononuclear cells of patients with inflammatory bowel diseases

“…Tumor necrosis factor (TNF)-α is a multifunctional cytokine involved in the advancement of inflammatory responses and is critical in the pathogenesis of inflammatory, autoimmune and malignant diseases (13). TNF-α is key in cell-mediated immunity, as demonstrated by high serum levels of TNF-α in IBD blood and tissue samples (14,15 3 and MOHAMMAD REZA ZALI majority of which are located in its promoter region and certain polymorphisms affect the expression level of the gene (16,17). The present study hypothesized that differences in cytokine levels are due to gene polymorphisms, which may have an important role in the inflammatory response and influence the pathophysiology of IBD.…”

The association analysis of TLR2 and TLR4 gene with tuberculosis in the Tibetan Chinese population

“…Previous studies have identified genes that confer disease susceptibility by regulating the immune response [ 4 , 5 ]. A twin study found that PTB concordance in identical twins is2-fold higher than that in non-identical twins [ 6 ].…”

Correlation between MBL2/CD14/TNF-α gene polymorphisms and susceptibility to spinal tuberculosis in Chinese population

“…Moreover, in the clinical course of human TB, high levels of TNF-α have been associated with clinical decline in patients with TB, and higher secretion of TNF-α in humans could be associated with the haematogenous dissemination of M. tuberculosis to other organs [ 36 , 37 ]. The TNF-α −308 G/A polymorphism was found to protect against TB in Sicily and the −308A-238G haplotype was protective in Colombia [ 38 ]. However, any association of TNF-α with spinal TB in the Chinese population has not been reported.…”