Significant Growth by Species Within Human Macrophage-Like Cells Is a Phenotype Correlated with the Ability to Cause Disease in Mammals

are significant sources of tick-borne diseases in humans worldwide. In North America, two species in the spotted fever group of have been conclusively associated with disease of humans: , the causative agent of Rocky Mountain spotted fever, and , the cause of rickettsiosis. Previous work in our lab demonstrated non-endothelial parasitism by another pathogenic SFG species, , within THP-1-derived macrophages, and we have hypothesized that this growth characteristic may be an underappreciated aspect of rickettsial pathogenesis in mammalian hosts. In this work, we demonstrated that multiple other recognized human pathogenic species of , including , , , and can grow within target endothelial cells as well as within PMA-differentiated THP-1 cells. In contrast, , a species not associated with disease of humans, and strain Iowa, an avirulent derivative of pathogenic , could invade both cell types but proliferate only within endothelial cells. Further analysis revealed that similar to previous studies on , other recognized pathogenic species could grow within the cytosol of THP-1-derived macrophages and avoided localization with two different markers of lysosomal compartments; LAMP-2 and cathepsin D. , on the other hand, demonstrated significant co-localization with lysosomal compartments. Collectively, these findings suggest that the ability of pathogenic rickettsial species to establish a niche within macrophage-like cells could be an important factor in their ability to cause disease in mammals. These findings also suggest that analysis of growth within mammalian phagocytic cells may be useful to predict the pathogenic potential of newly isolated and identified species.