Macrophages and tuberculosis

Mycobacterium tuberculosis and M. bovis, the causative agents of human and bovine tuberculosis (TB), respectively, have evolved efficient and potent mechanisms to enable their survival within macrophages. In particular, by preventing the fusion of phagosomes with lysosomes, mycobacteria are able to regulate their environment, free from acidification and lysosomal hydrolases. The bacilli are also able to hijack the cytokine responses of the macrophage and dampen the host's protective immune responses, promoting the secretion of anti-inflammatory cytokines and dampening TNF-α-dependent host protective responses. In turn, macrophages have developed ways to overcome these restraints imposed by the bacteria. Induction of autophagy by environmental stresses, such as nutrient or growth factor deprivation, Th1 cytokines (TNF-αand IFN-γ ) and pathogen-associated molecular patterns (PAMPs) leads to the intracellular elimination of mycobacteria by macrophages. In addition, autophagy is potentially involved in antigen processing and presentation and regulates the secretion of some cytokines. Finally, some receptors and their signalling molecules, including Tolllike Receptor (TLR)2 and TLR4, the scavenger receptor MARCO and MyD88 have been shown to be important in host-protective responses. This review summarises the current literature regarding the close and pivotal interactions between macrophages and mycobacteria that, in turn, determine the outcome of infection with these important intracellular pathogens.