Pathogenicity and immunity in human infections with the tick-borne bacterium "Candidatus Neoehrlichia mikurensis

Candidatus (Ca.) Neoerhlichia (N.) mikurensis is an emerging tick-borne pathogen of humans that gives rise to the infectious disease neoehrlichiosis. We have recently succeeded in cultivating this obligate intracellular bacterium onto endothelial cell lines.

The apparent tropism of the bacteria for vascular endothelium may explain the high frequency of vascular events associated with neoehrlichiosis. The specific aims of this project are To establish that Ca. N. mikurensis gives rise to infectious vasculitis. FISH is used to detect bacteria in vascular endothelium in biopsies.

The infectious cycle of the bacteria in infected endothelial cells is studied by electron microscopy, proteomics and immunocytochemistry.To prove that Ca. N. mikurensis is a chronic latent infection that reactivates when immune defenses are lowered.

Malignant lymphoma patients treated with rituximab are monitored for reactivation of the infection and levels of specific T cells thar produce  Interferon-gamma.To elucidate the protective and pathogenic functions of B cells in neoehrlichiosis.

Immunocompromised and immuncompetent patients are compared regarding B cell subsets (mass cytometry), antibody levels, and autoantibodies against endothelium and erythrocytes.To determine if Ca. N. mikurensis can cause atypical vasculitis and autoimmune hemolytic anemia.To sequence and annotate the genome of Ca.

N. mikurensis and do comparative genomics. 10X chromium technique and Hi-illumina sequencing is used.