Rickettsial infections.
Rickettsiae are obligate intracellular alpha-proteobacteria that primarily target the microvascular endothelium. In the last two decades, new rickettsial pathogens have been associated with human illness around the world. Clinically, the common denominator in all rickettsioses is the development of increased microvascular permeability, leading to cerebral and non-cardiogenic pulmonary edema. With the development of powerful research tools, advances in the understanding of rickettsial pathogenesis have been dramatic. Entry into the host cell is followed by rapid escape into the cytoplasm to avoid phagolysosomal fusion. Spotted fever group rickettsiae induce actin polymerization via a group of proteins called RickA, which promote nucleation of actin monomers via the Arp2/3 complex at one rickettsial pole, propelling the bacteria across the cytoplasm and into neighboring cells. Damage to the host cell is most likely multifactorial. The most extensively studied mechanism is the generation of reactive oxygen species (ROS) and downregulation of enzymes involved in protection against oxidative injury. The significance of ROS-mediated cellular damage in vivo is beginning to be elucidated. The main pathogenic mechanism is increased microvascular permeability leading to profound metabolic disturbances in the extravascular compartment. The underlying factors responsible for those changes are beginning to be elucidated in vitro and include direct effects of intracellular rickettsiae, cytokines, and possibly activated coagulation factors--all of which most likely modify interendothelial junctions. Our knowledge on rickettsial pathogenesis will continue to expand in the near future as new research tools become available.
Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555-0609, USA. jolano@utmb.edu
Juan P
JP
Olano
D000818:Animals; D006801:Humans; D012287:Rickettsiaceae / Q000145:classification / Q000276:immunology / Q000472:pathogenicity; D012288:Rickettsiaceae Infections / Q000276:immunology* / Q000382:microbiology*