Sensing of Mycobacterium tuberculosis and consequences to both host and bacillus

Abstract

Mycobacterium tuberculosis (Mtb), the primary causative agent of human tuberculosis, has killed more people than any other bacterial pathogen in human history and remains one of the most important transmissible diseases worldwide. Because of the long-standing interaction of Mtb with humans, it is no surprise that human mucosal and innate immune cells have evolved multiple mechanisms to detect Mtb during initial contact. To that end, the cell surface of human cells is decorated with numerous pattern recognition receptors for a variety of mycobacterial ligands. Furthermore, once Mtb is ingested into professional phagocytes, other host molecules are engaged to report on the presence of an intracellular pathogen. In this review, we discuss the role of specific mycobacterial products in modulating the host's ability to detect Mtb. In addition, we describe the specific host receptors that mediate the detection of mycobacterial infection and the role of individual receptors in mycobacterial pathogenesis in humans and model organisms.

Keywords: Mycobacterium tuberculosis; innate immunity; microbial pathogenesis; pattern recognition receptors.

Fig. 1. Schematic representation of the Mycobacterium tuberculosis (Mtb) cell wall

Components of the Mtb cell wall are ligands for PRRs, including peptidoglycan, LAM and its variants, mycolic acids, and lipoproteins. Secreted proteins, c-diAMP, and extracellular DNA are also recognized by host PRRs.

Fig. 2. Pattern recognition receptors important for the sensing of mycobacterial PAMPs

This schematic shows the major receptors involved in recognition of Mtb and their localization to the surface or the cytoplasm of host cells. PRRs on the surface of cells include TLRs, scavenger receptors, and c-type lectin receptors. Cytoplasmic receptors recognize mycobacterial components, such as secreted proteins and DNA that access the cytoplasm through phagosomal membrane damage. Major signaling pathways are shown including NFκB- and IRF3-dependent cytokine secretion, inflammasome-mediated IL-1β secretion, and the activation of autophagy.