Host-cell interactions with pathogenic Rickettsia species

Abstract

Pathogenic Rickettsia species are Gram-negative, obligate intracellular bacteria responsible for the spotted fever and typhus groups of diseases around the world. It is now well established that a majority of sequelae associated with human rickettsioses are the outcome of the pathogen's affinity for endothelium lining the blood vessels, the consequences of which are vascular inflammation, insult to vascular integrity and compromised vascular permeability, collectively termed 'Rickettsial vasculitis'. Signaling mechanisms leading to transcriptional activation of target cells in response to Rickettsial adhesion and/or invasion, differential activation of host-cell signaling due to infection with spotted fever versus typhus subgroups of Rickettsiae, and their contributions to the host's immune responses and determination of cell fate are the major subtopics of this review. Also included is a succinct analysis of established in vivo models and their use for understanding Rickettsial interactions with host cells and pathogenesis of vasculotropic rickettsioses. Continued progress in these important but relatively under-explored areas of bacterial pathogenesis research should further highlight unique aspects of Rickettsial interactions with host cells, elucidate the biological basis of endothelial tropism and reveal novel chemotherapeutic and vaccination strategies for debilitating Rickettsial diseases.

Figure 1. NF-κB inhibition via attenuation of proteasome activity by MG132 treatment during Rickettsia rickettsii infection of human umbilical vein endothelial cells induces apoptotic cellular events

Endothelial cells (ECs) were either incubated for 6 h with culture medium alone and medium containing MG132 or were infected in the absence and presence of MG132. Treatment with staurosporine or etoposide was used as a positive control for induction of apoptosis. (A & B) show fragmentation of cellular DNA and changes in nuclear morphology as observed under a fluorescent microscope after TUNEL and Hoechst 33258 staining, respectively. Yellow arrows point towards cells with normal nuclear structure while white arrows indicate TUNEL-positive cells in (A) and condensed nuclei correlating with induction of apoptosis in (B). Original magnification ×20. Bar = 10 μm. C: Culture medium alone; ETP: Treatment with etoposide; MG: Medium containing MG132; Rr: Infected in the absence of MG; STS: Treated with staurosporine. Reproduced with permission from [99].