Rickettsial diseases: from Rickettsia-arthropod relationships to pathophysiology and animal models

Rickettsiae cause spotted fevers and typhus-related diseases in humans. Some of these diseases occur worldwide and are life-threatening, for example, epidemic typhus is still a major health problem despite the apparent efficiency of antibiotic treatment. In addition, Rickettsia prowazekii, the agent of epidemic typhus, and R. rickettsii, the agent of Rocky Mountain spotted fever, are microorganisms that could potentially be used as bioweapons to induce panic in the population. Rickettsiae are obligate intracellular bacteria in both vertebrate and invertebrate hosts, but rickettsial species differ in terms of association with arthropods, behavior of the vector to infection, pathophysiology and outcome of the disease. Understanding the pathogenic steps of rickettsioses is essential to develop protective strategies against these bacteriological threats. Unfortunately, the mechanisms involved in the pathogenesis of many rickettsioses are poorly characterized, and protective immunity is incompletely understood, in part because accurate animal models that mimic human diseases are lacking. In the past, murine models have been of limited value because infection of mice was without effect or resulted in erratic mortality. Recent studies have reported that rickettsial infection can be established in mice, depending on the genetic background of mice, the type of rickettsial species and the route of inoculation. These models may be useful for analyzing the pathogenesis of rickettsioses, especially epidemic typhus, evaluating new therapeutic molecules and vaccine candidates, and preventing future outbreaks.