Immune response gene polymorphisms in tuberculosis

Abstract

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (M.tb), remains a leading public health problem in most parts of the world. Despite the discovery of the bacilli over 100 years ago, there are still many unanswered questions about the host resistance to TB. Although one third of the world's population is infected with virulent M.tb, no more than 5-10% develop active disease within their lifetime. A lot of studies suggest that host genetic factors determine the outcome of M.tb-host interactions, however, specific genes and polymorphisms that govern the development of TB are not completely understood. Strong evidence exists for genes encoding pattern recognition receptors (TLR, CD14), C-type lectins, cytokines/chemokines and their receptors (IFN-γ, TNF-α, IL-12, IL-10, MCP-1, MMP-1), major histocompatibility complex (MHC) molecules, vitamin D receptor (VDR), and proton-coupled divalent metal ion transporters (SLC11A1). Polymorphisms in these genes have a diverse influence on the susceptibility to or protection against TB among particular families, ethnicities and races. In this paper, we review recent discoveries in genetic studies and correlate these findings with their influence on TB susceptibility.

Association of Interleukins Genes Polymorphisms with Multi-Drug Resistant Tuberculosis in Ukrainian Population

“…It is well known that IL-2 has an impact on macrophages activation and direct cytotoxicity of T-cells, which accounts for protective role of IL-2 against tuberculosis [23]. On the contrary, it supports the activation of phagocytic elimination of MTB [24].…”

Assessment of treatment response in tuberculosis

“…There is considerable heterogeneity observed in the immune response to tuberculosis with a myriad of host and microbial related factors playing a role in inter-individual and geographic variation in the measured immune response to MTB [96]. Whilst biomarkers should ideally be generalizable across ethnically diverse populations, there is evidence that they need to be tailor-made to specific sub-groups.…”

HLA Loci and Respiratory Infectious Diseases

“…Also, the susceptibility for a pulmonary tuberculosis infection was found to be associated with the TNF-α -857T/C genetic polymorphism in Asian populations [90] and, for a reduced risk, with the CD14 G(-1145)A and C(-159)T polymorphisms in Chinese Han population [91] . However, no association was observed between TNF polymorphisms and TB in several other populations, such Indian, Cambodian, Thais or Turkish [92][93][94][95] . Additionally, the use of TNF inhibitors in therapies against autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, psoriatic arthritis and psoriasis, has been associated to an increase in TB risk [96,97] .…”