The role of ATG5-dependent autophagy during Rickettsia australis infection. (INC4P.339)

Abstract

Abstract Rickettsiae are obligate intracellular bacteria that replicate in the cytoplasm of eukaryotic cells. We found that degradative autophagy is induced upon the infection of murine bone marrow macrophages (BMMs) with R. australis and the bacteria are specifically targeted by autophagosomes for degradation. Inhibition of autophagy using 3-methylamine (3-MA) significantly increased bacterial burden in BMMs. Consistently, rickettsial loads in livers of infected Atg5flox/flox Lyz-Cre mice were significantly greater than those of Atg5flox/flox littermates. As a consequence, host survival was significantly reduced in autophagy-deficient Atg5flox/flox Lyz-Cre animals, suggesting that macrophage autophagy mediates host cellular immunity against rickettsiae in vivo. In contrast, limited level of autophagy was induced in human endothelial cells, which are the major targets of rickettsiae. Taken together, our results suggest that R. australis induces autophagy in murine macrophages and plays a role in bacterial clearance both in vitro and in vivo. However, levels of autophagy in human endothelial cells early during infections appear to be lower compared to those in murine macrophages.