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.

Rickettsia rickettsiiInfection of Human Macrovascular and Microvascular Endothelial Cells Reveals Activation of Both Common and Cell Type-Specific Host Response Mechanisms

“…Pathogenic rickettsiae display tropism for vascular endothelial cell lining of small and mediumsized blood vessels in their mammalian hosts. As a consequence, the predominant pathological features of resultant clinical syndromes-for example, Rocky Mountain spotted fever due to Rickettsia rickettsii-are generally attributed to altered vascular functions due to preferential infection of the endothelium (27,36). However, despite critical contributions of endothelial injury, inflammation, and dysfunction to the pathogenesis of vasculotropic rickettsioses, the biological basis of rickettsial interactions with microvascular endothelium of vertebrate hosts still remains poorly understood.…”

Severe Condition of Scrub Typhus Meningo-Encephalitis in a Child:A Case Report from Delhi, India

“…Rickettsial diseases are caused by intracellular parasites which are pathophysiologically associated with vascular endothelium and reticuloendothelial cells [1]. One such rickettsial disease is scrub typhus, an important cause of fever of unknown origin in all age groups particularly in children [2].…”

Changes of Bcl-2, Bax and Caspase-3 expression in the dermal microvascular endothelial cells and the epidermal layers of the eschar (tache noire) in patients with Mediterranean spotted fever

“…Rickettsiae are obligate intracellular parasites with prominent tropism for the host vascular endothelial cells [3,4]. The rickettsial diseases are still not quite thoroughly studied as to some aspects of their pathogenesis and especially to issues that concern the crucial signals for apoptosis in the targeted microvascular endothelial cells [4][5][6].…”

“…To survive, rickettsiae are capable of either inducing or inhibiting apoptosis during different stages of infection [4,[7][8]. The programmed cell death in MSF is among the www.fhc.viamedica.pl phenomena that are still inadequately elucidated [4][5][6]9].…”

“…The programmed cell death in MSF is among the www.fhc.viamedica.pl phenomena that are still inadequately elucidated [4][5][6]9]. We were prompted to conduct the present study by the scantiness of studies on apoptosis in the microvascular endothelial cells in rickettsial diseases and by practically nonexistent research on patients with MSF [10][11][12][13].…”