Genetic variability of Anaplasma phagocytophilum
Anaplasma phagocytophilum is an obligat intracellular bacterium that replicates in neutrophil granulocytes and causes febrile disease in humans and animals. In Europe, it is transmitted by Ixodes ricinus ticks. It In contrast to North America, human granulocytic anaplasmosis is a rare disease in Europe. Further, cross-infection experiments showed that A. phagocytophilum isolates of distinct host origin are not uniformly infectious for heterologous hosts. This led to several approaches of genetic characterization of A. phagocytophilum strains looking for molecular markers that could be associated with geographic origin or host species. Since a variety of target genes was used previously, we developed a standardized multilocus sequence typing (MLST) scheme for A. phagocytophilum (http://pubmlst.org/). We could show that all strains from humans, dogs and horses belonged to the same clonal complex. Since granulocytic anaplasmosis in these animals is often diagnosed in Europe, most human cases might not be recognized. We currently characterize further strains by means of MLST and try to sequence whole genomes.
Immunological control of Anaplasma phagocytophilum
Since A. phagocytophilum replicates in a main cell of the innate immune system, it is used as model organism to study the immunological control of obligat intracellular pathogens. We showed using the mouse model that the control in the early phase of infection is IFN-γ-dependent. In contrast, CD4+ T-cells are indispensable for bacterial elimination. To date, the effector mechanisms used by CD4+ T-cells are unclear because mice with defects for Th1 cytokines, perforin and Fas/Fas ligand were fully able to clear the infection. Therefore, we are studying in vitro whether a direct interaction between CD4+ T-cells and A. phagocytophilum infected granulocytes inhibits bacterial replication. For this purpose we use in vitro generated murine neutrophil granulocytes. Further, we use granulocytes defective for MHC I and MHC II to analyze whether antigen presentation by neutrophils is need for CD4+ T-cell dependent control. Respective gene-deficient cell lines are used to study whether neutrophils itself contribute to the defense against A. phagocytophilum.
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Huhn C., Winter C., Wolfsperger T., Wueppenhorst N., Smrdel K. S., Skuballa J., Pfaefle M., Petney T., Silaghi C., Dyachenko V., Pantchev N., Straubinger R. K., Schaarschmidt-Kiener D., Ganter M., Aardema M. L., von Loewenich F. D.. Analysis of the Population Structure of Anaplasma phagocytophilum Using Multilocus Sequence Typing. PLOS ONE. 2014; 9(4).