Chapter 10 - Mycobacterial Survival in Alveolar Macrophages as a Result of Coronin-1a Inhibition of Autophagosome Formation

Abstract

Alveolar macrophages are the lung’s first line of defense against infection by pathogenic microbes. Despite this, Mycobacterium tuberculosis can proliferate in alveolar macrophages by inhibiting phagolysosome biogenesis. Differential recruitment of Rab GTPases, which regulate phagosome maturation, to mycobacterial phagosomes contributes to the inhibition of phagolysosome biogenesis. Recruitment of Coronin-1a, an actin binding protein, to mycobacterial phagosomes is also thought to inhibit their fusion with lysosomes. Host defense mechanisms exploit autophagy to control the proliferation of intracellular pathogens, including M. tuberculosis. On the other hand, several intracellular bacteria can evade the elimination induced by the autophagic process. M. tuberculosis also escapes being targeted for autophagosomal uptake. We have demonstrated that the depletion of Coronin-1a inhibits mycobacterial survival in macrophages, since Coronin-1a depletion facilitates the formation of autophagosomes around mycobacterial phagosomes. These results suggest that Coronin-1a inhibits autophagosome formation in regard to M. tuberculosis, thereby allowing mycobacterial survival in alveolar macrophages.