Host-pathogen interactions during Mycobacterium tuberculosis infections

The intimate and persistent connection between Mycobacterium tuberculosis and its human host suggests that the pathogen has evolved extensive mechanisms to evade eradication by the immune system. In particular, the organism has adapted to replicate within phagocytic cells, especially macrophages, which are specialized to kill microbes. Over the past decade of M. tuberculosis research, the means to manipulate both the organism and the host has ushered in an exciting time that has uncovered some of the mechanisms of the innate macrophage-pathogen interactions that lie at the heart of M. tuberculosis pathogenesis, though many interactions likely still await discovery. In this chapter, we will delve into some of these advances, with an emphasis on the interactions that occur on the cellular level when M. tuberculosis cells encounter macrophages. In particular, we focus on two major aspects of M. tuberculosis biology regarding the proximal physical interface between the bacterium and host, namely the interactions with the phagosomal membrane as well as the distinctive mycobacterial cell wall. Importantly, some of the emerging paradigms in M. tuberculosis pathogenesis and host response represent common themes in bacterial pathogenesis, such as the role of host cell membrane perforation in intracellular survival and host response. However, the array of unique bacterial lipid mediators and their interaction with host cells highlights the unique biology of this persistent pathogen.