Autophagy protects against infection and inflammation in a murine model of tuberculosis (158.9)

Abstract Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis, infects approximately one-third of the world’s population. Recently, autophagy, an intracellular process that sequesters portions of the cytoplasm, including damaged or surplus organelles into autophagosomes and degrades them upon fusion with lysosomes, was found to be crucial in macrophages for controlling MTB ex vivo. Additionally, the autophagy pathway and proteins have been shown to be critical in immunity and inflammation. Despite the known roles of autophagy in killing intracellular bacteria and regulating the immune system it is unknown how autophagy controls MTB in vivo. Using Atg5f/f LyzM-Cre mice, we investigated the in vivo role of autophagy in macrophages in controlling MTB infection and shaping the immune response. Compared to wild-type mice, Atg5f/f LyzM-Cre mice displayed greater weight loss, lung pathology and death in a dose-dependent manner. An increase in neutrophils and macrophages was found in the lung of infected Atg5f/f LyzM-Cre mice whereas the wild type mice had an increase in CD4 and CD8 T cell infiltrates. In this context, luminex assay also revealed an increase in IL-1α, GM-CSF, IL-17 and CXCL1 in the lung lavage of the infected Atg5f/f LyzM-Cre mice when compared to the wild type mice. Taken together, these results show the importance of the autophagy pathway in macrophages in vivo in controlling MTB infection, and indicate a broader role in shaping the immune response.