By

ii Human granulocytic anaplasmosis (HGA), an emerging tick-borne zoonosis is caused by a gram-negative, obligatory intracellular bacterium, Anaplasma phagocytophilum. A. phagocytophilum has the remarkable ability to inhibit the spontaneous apoptosis of neutrophils, block the production of reactive oxygen intermediates, and replicate in membrane-bound inclusions in the cytoplasm of neutrophils. However, the A. phagocytophilum inclusions have not been fully characterized, and bacterial factors contributing to these phenomena remain unknown. In this study, we studied several molecular aspects of A. phagocytophilum pathogenesis. (1) Characterization of A. phagocytophilum replicative inclusions. We demonstrated that A. phagocytophilum replicative inclusions had the characteristic of early autophagosomes, as shown by the presence of autophagosome markers, LC3 and double lipid bilayer membrane in the A. phagocytophilum inclusions. Furthermore our data suggested that autophagy enhanced A. phagocytophilum replication instead o