Human Granulocytic Anaplasmosis (HGA) is a tickborne disease which infects both mouse and human hosts. The agent of HGA, Anaplasma phagocytophilum, preferentially infects and replicates within circulating neutrophils. Because neutrophils primarily function to destroy infectious bacteria and possess a very brief lifespan, this host specificity is highly unusual. Our research examines the mechanisms by which A. phagocytophilum evades destruction by the neutrophilâ??s microbicidal machinery and propagates between host neutrophils. In particular, the aim was to investigate how A. phagocytophilum alters and takes advantage of the neutrophil's response to vascular inflammation.



A neutrophilic cell line infected with Anaplasma phagocytophilum exhibits colonies of the bacterium within the cytoplasm.

A major aim of our research is to determine how binding of A. phagocytophilum to the cell surface affects the inflammatory responses of neutrophils. Because A. phagocytophilum is known to decrease selectin expression and reduce production of superoxide production in neutrophils we hypothesized that bacterial binding would diminish acute arrest and migration of neutrophils during recruitment to a model of inflamed endothelium. To test this hypothesis, we exposed human neutrophils to A. phagocytophilum or E. Coli in a flow chamber coated with an E-selectin expressing cell line. Migration in neutrophils exposed to A. phagocytophilum was significantly lower than those expressed to E-coli. Measurement of intracellular calcium indicate that calcium flux is suppressed in neutrophils exposed to A. phagocytophilum, suggesting that A. phagocytophilum inhibits neutrophil migration but not arrest through a calcium dependent pathway. We seek to determine whether A. phagocytophilum suppresses calcium flux and migration in order to maintain infected neutrophils in the bloodstream where neutrophil to neutrophil transmission is likely to occur, rather than within surrounding tissues.