Innate immune recognition of Mycobacterium tuberculosis

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a major health problem, with 10 million new cases diagnosed each year. Innate immunity plays an important role in the host defense against M. tuberculosis, and the first step in this process is recognition of MTB by cells of the innate immune system. Several classes of pattern recognition receptors (PPRs) are involved in the recognition of M. tuberculosis, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), and Nod-like receptors (NLRs). Among the TLR family, TLR2, TLR4, and TLR9 and their adaptor molecule MyD88 play the most prominent roles in the initiation of the immune response against tuberculosis. In addition to TLRs, other PRRs such as NOD2, Dectin-1, Mannose receptor, and DC-SIGN are also involved in the recognition of M. tuberculosis. Human epidemiological studies revealed that genetic variation in genes encoding for PRRs and downstream signaling products influence disease susceptibility, severity, and outcome. More insight into PRRs and the recognition of mycobacteria, combined with immunogenetic studies in TB patients, does not only lead to a better understanding of the pathogenesis of tuberculosis but also may contribute to the design of novel immunotherapeutic strategies.

Figure 1

The structure of the Mycobacterium tuberculosis cell wall. This figure shows a schematic representation of the major components of the cell wall and their distributions. The inner layer is composted of peptidoglycan which is covalently linked to arabinogalactan layer. The outer membrane contains mycolic acids, glycolipids like (mannose-capped) lipomannan, and mannoglycoproteins.

Figure 2

Pattern recognition receptors in the recognition of mycobacteria and downstream signaling pathways. Mycobacteria can be recognized through different pattern recognition receptors (PRRs) of the host. Both intracellular and extracellular receptors are involved in this process. After recognition of mycobacteria, intracellular signaling cascades are activated which eventually will lead to the activation of transcription of NF-κB. After transcription, the production of pro- and anti-inflammatory cytokines and chemokines is induced. The type of signaling cascade induced depends mainly on the type of PRR that recognizes (components of) MTB.