Toll Like Receptor-2 Signaling in Mycobacterium Tuberculosis Infection-A Double-Edged Sword

摘要

Mycobacterium tuberculosis (MTB), one of the major health concerns to date, is known to survive in antigen-presenting cells including macrophages. Macrophages process the antigens where the extent of microbicidal action mainly depends on the Toll like receptor-2 (TLR2). TLR2signaling involving MyD88, NF-kp, ERK1/2 and p38 MAPK is an integral part of the host immune response against mycobacterial infection. But it is also exploited by MTBfor immune evasion which raises a question whether TLR2 acts as a 'friend' or 'foe' to the host. The MTBcell wall is rich in components that act as TLR2agonists such as lipoproteins like LpqH, LprA, LprG, PhoSl and glycolipids like Man-LAM, LM, PIM and TDM. A number of new MTB antigens are being recognized as TLR2 agonists like PE and PPE family of proteins, secretory proteins, heat shock proteins, certain latency and resuscitation proteins like DATIN, MymA and RpfB. The engagement of TLR2 with these ligands results in the elaboration of Thl type protective proinflammatory cytokines like TNF-a and IL-12. However, prolonged signaling of TLR2by such molecules also leads to the inhibition of phagosomal maturation, resistance to innate microbicidal mechanisms and diminished MHC Class II antigen-processing and presentation. Among these inhibiting the recognition of infected macrophages by CD4+ T cells contributes markedly to the immune evasion mechanism leading to MTB survival inside the antigen-presenting cell. Understanding the interaction between MTB and TLR2and its contribution to the immune response or to the immune evasion will help in finding new ways to eliminate MTB infection.