Examples include variants of TLR4 in sepsis, malaria, inflammatory bowel disease and atherosclerosis; variants in TLR2 in tuberculosis and asthma; a variant in Mal (a key signal for TLR2 and TLR4) in malaria, tuberculosis and systemic lupus erythematosus; and variants in the kinase IRAK4 in pyogenic infections.
Furthermore, the levels of TLR2, TLR4 and IFN-γ mRNA expression were marked increased in the tuberculous PE when compared with the correspondent serum.
TLR2rs5743708 subgroup analysis identified the A allele to increase susceptibility to TB in the Asian ethnic group, while conferring protection in the Hispanic group.
Coinheritance of these polymorphisms with previously identified risk alleles in Toll-like receptor 2 and TIRAP was associated with an additive risk of tuberculosis susceptibility.
Animal studies have shown that TLR2-knockout mice are more susceptible to septicemia due to Staphylococcus aureus and Listeria monocytogenes, meningitis due to Streptococcus pneumoniae, and infection with Mycobacterium tuberculosis, suggesting that functional TLR2 polymorphisms may impair host response to a certain spectrum of microbial pathogens.
Our data suggest that the S/M genotype of the microsatellite (GT)n polymorphisms in intron 2 of the TLR2 gene may increase susceptibility to TB in Chinese, and the S/L genotype may act as a negative risk factor.
Material from M. tuberculosis and P. acne has been repeatedly detected in the sarcoidosis lesions, implying the involvement of the Toll-like receptor2 (TLR2) gene that responds to these intracellular pathogens.
Information on expression of TLR-2, myeloid differentiation factor (MyD88), IL-1R- associated kinase-4 (IRAK4) and nuclear factor kappa B (NF-kB) in HIV+LTBI+ and HIV+ patients with active TB disease is limited.
The adaptor protein TIRAP mediates down stream signalling of TLR2 and 4, and polymorphisms in the TIRAP gene (TIRAP) have been associated with susceptibility and resistance to tuberculosis (TB) in adults.
In the present study, we investigated direct immune responses of PMCs against two mycobacterial strains, M. bovis vaccine strain Bacille Calmette-Guérin (BCG) and M. tuberculosis virulent strain H37Rv, and the role of TLR2 in such responses.
Of note, network analysis comparing TB-associated host genes identified in the current HIV-negative TB cohort to TB-associated genes identified in our previously published Ethiopian HIV-positive TB cohort, revealed an over-representation of pattern recognition receptors including TLR2 and TLR4 in the HIV-positive cohort which was not seen in the HIV-negative cohort.
CD1c<sup>+</sup>CD11b<sup>+</sup> DC subset from tuberculous pleural effusions expressed higher levels of TLR2, TLR4, CD172a, CD206 and FcεRⅠ, but lower levels of CD80, CD83 and CD86 compared with CD1c<sup>+</sup>CD11b<sup>-</sup> DC subset.
Polymorphisms of the toll-like receptor 2 (TLR2) gene (Arg677Trp, Arg753Gln) and the TLR4 gene (Asp299Gly, Thr399Ile) were investigated in 205 tuberculosis (TB) patients and 203 controls.
Collectively, these findings demonstrated that miR-23a-5p modulated the innate host defense by promoting mycobacteria survival and inhibiting the activation of autophagy against M.tb. through TLR2/MyD88/NF-κB pathway by targeting TLR2, which may provide a promising therapeutic target for tuberculosis.