Pattern Recognition Receptors and Cytokines in Mycobacterium tuberculosis Infection—The Double-Edged Sword?

Figure 2

Immune recognition of M. tuberculosis during phagocytosis. Several pattern recognition receptors (PRRs) on phagocytic cells have been identified for the recognition of conserved pathogen associated molecular patterns (PAMPs) of mycobacteria. TLR2 recognizes the 19 kDa lipoprotein (LP), lipomannan (LM), and lipoarabinomannan (LAM). TLR1-TLR2 and TLR6-TLR2 heterodimers bind diacylated and triacylated LP, respectively. TLR4 binds tri- and tetra-acylated LM, heat shock protein 65 (HSP65), and 50S ribosomal protein (50S RP), whereas mycobacterial DNA is recognized by phagosomal TLR9. Complement receptors (CRs) are mainly responsible for uptake of opsonized M. tuberculosis, while mannose receptors (MRs) and scavenger receptors (SR) are for uptake of nonopsonized M. tuberculosis. Cytosolic receptor NOD2 interacts with Mtb derived peptidoglycan component muramyl dipeptide (Mtb-MDP). MyD88 is the key component in TLR-mediated defense mechanism whose downstream signaling cascade leads to the activation of NF-𝜅B transcription factor and to the production of inflammatory molecules. TLRs are expressed on phagocytic cell surface and in phagosomes. Dashed arrow represents the presence of numerous signaling molecules in between.