Rickettsial Infections

Abstract

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.

Syndromic classification of rickettsioses: an approach for clinical practice

“…In this regard, and with the exception of Rickettsia prowazekii, the human is usually an accidental host. 4 From the first description of R. prowazekii as an etiological agent of epidemic typhus in 1916 up to the late 1980s, eight further species were described as causes of rickettsioses around the world: Rickettsia rickettsii, Rickettsia typhi, Rickettsia conorii subsp. conorii, Rickettsia akari, Rickettsia sibirica, Rickettsia australis, Rickettsia conorii subsp.…”

Recent Molecular Insights into Rickettsial Pathogenesis and Immunity

“…Follow-up studies to identify upstream signaling mechanisms further reveal an essential role for NF-κB activation in the maintenance of mitochondrial integrity, maintenance of the balance between pro- and anti-apoptotic proteins, and prevention of activation of caspase cascade during R. rickettsii infection of cultured human endothelial cells [69]. In addition, ample published evidence also suggests that endothelial cells infected with R. rickettsii or R. conorii display induced expression of prothrombotic, proadhesive and proinflammatory genes, the hallmark features of ‘endothelial activation’ (summarized in Figure 1 and [3,42–44,69,70]). Originally discovered and identified for their roles in antiviral defense, interferons are key signaling cytokines now established as primers, activators and inhibitors of innate and adaptive immune responses.…”

Rickettsia Species: Rickettsioses

“…Rapid escape into the cytoplasm occurs prior to phagolysosomal fusion. This process is mediated by the up-regulation of genes encoding for membranes with membranolytic activity like tlyC (hemolysin) and pld (phospholipase D) [89].…”