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Background: Tuberculosis (TB), an infectious disease caused by Mycobacterium Tuberculosis (MTB). Toll-like receptors (TLRs) are the best-studied class of PRRs, and they recognize specific pathogen-associated molecular patterns (PAMPs) from various microorganisms.  Objectives: This study aimed to determine and measure cellular TLR2 and TLR4 in active TB, latent TB and healthy individuals. Also aimed to define correlation between gene expression and present of TLR4 and TLR2 in study volunteers.  Materials & Methods: This Multi-site, prospective unmatched age and sex case-control, hospital and community-based study. 244 Consented volunteersor patients diagnosed as active tuberculosis, diagnosed latent TBI and a community controls volunteers with negative both TST and INF γ release assay were enrolled. Three-color Flow cytometry using Heparinized blood to study surface expression of TLR4 (CD284) and TLR2 (CD282), by Mean channel fluorescence intensity (MFI). EDTA blood was used for mRNA expression of both receptors using Quantitative RT-PCR.  Results: TLR2, TLR4 cell surface expression by Flow cytometry was decreased in all study volunteers with no significance differences (p.value 0.24).mRNA expression of TLR2 were increased in active TB compared to Latent TBI and healthy individuals,while mRNA TLR4 decreased in active TB and showed increased pattern in latent and low level of expression in healthy volunteers, associated with no significant difference in the expression of TLR-2 mRNA between patients and close contacts with LTBI (p. value 0.045), compared with significance correlation between cellular TLR2 and expression and BCG status (p. value 0.00) respectively. There was highly significance correlation between TST indurations and level of both TLR2 and TLR4 (p. value 0.00). Also there was significant correlation between mRNA expression of TLR2 and disease types (p value 0.01). Single Nucleotide Polymorphisms (SNPs) in TLR2and TLR4,in active Tb Patients Showed three alleles,group one were heterozygous allele, homozygous wild type in group two, while homozygous mutant present in group three with statistical significant with disease stages, (P.value 0.02), while LTBI volunteers had only homozygous mutant present and group two had undetermined alleles, and four of them develop active TB infection, while healthy controls had similar alleles.  Conclusion: Up-regulation of TLR-2 and TLR-4 due to SNPs may be involved in the process of tuberculosis infection in Sudanese individuals.

Role of Toll Like Receptor 2 and 4 (TLR2 and TLR4) in Susceptibility and Resistance to Mycobacterium Tuberculosis Infection among Sudanese Patients