Kurzfassung

Anaplasma phagocytophilum is a Gram-negative obligate intracellular bacterium that replicates in neutrophile granulocytes of its host. In Europe it is transmitted by Ixodes ricinus ticks. It elicits acute febrile diseases in humans, pet animals and livestock.
Because A. phagocytophilum replicates in the hostile environment of an innate immune cell, it can be used as a model organism to study the immunological control of obligate intracellular bacteria. In vivo analyses in the murine system...Anaplasma phagocytophilum is a Gram-negative obligate intracellular bacterium that replicates in neutrophile granulocytes of its host. In Europe it is transmitted by Ixodes ricinus ticks. It elicits acute febrile diseases in humans, pet animals and livestock.
Because A. phagocytophilum replicates in the hostile environment of an innate immune cell, it can be used as a model organism to study the immunological control of obligate intracellular bacteria. In vivo analyses in the murine system showed that interferon-gamma is essential for pathogen control in the early phase of infection, whereas bacterial elimination was strictly dependent on CD4 T-cells. To date it was not possible to define the effector mechanisms used by CD4 T-cells, because mice with defects for Th1 cytokines, perforin and Fas/Fas-ligand were unimpaired in infection control.
In the past, in vitro studies using murine neutrophil granulocytes were hindered by the fact that these cells are extremely short-lived and difficult to purify. Recently, a system was developed that allows the in vitro generation of neutrophil granulocytes from immortalized precursor cell lines. We plan to use these cells to investigate whether CD4 T-cells directly interact with neutrophil granulocytes to enhance their effector functions and to inhibit bacterial replication. Neutrophil granulocytes deficient for MHC I and MHC II will be utilized to analyze whether this kind of T-cell-dependent control requires antigen-presentation. Furthermore, we plan to study whether neutrophils are directly involved in the control of A. phagocytophilum using the respective gene-deficient neutrophil cell-lines.
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