Members of the Rickettsia genus are Gram negative, obligate, intracellular bacteria with a life cycle that involves both an arthropod vector and a vertebrate host. Mammals constitute the principle reservoir with humans considered incidental hosts. Humans become infected from bites of infected ticks.
Rickettsial Host Interactions
Following a tick bite which causes direct inoculation into the blood vessels, Rickettsial bacteria penetrate the vascular endothelial cells by a receptor-mediated endocytic pathway. Rickettsial bacteria express Outer membrane protein B (rOmpB) which binds to host cell receptor Ku70 expressed on the surface of vascular endothelial cells. Via an enzymatic cascade, actin is polymerized which is necessary for the internalisation of the bacteria. The cell membrane then invaginates and phagocytosis of the bacterium occurs resulting in a phagosome.
The cell membrane of the phagosome is lysed and the bacteria are then able to escape into the cytosol where they move via actin filaments. The bacteria are then also able to penetrate adjacent cells through plasma membranes.
Pathogenesis of Rickettsial disease
In Rickettsial disease the bacteria stimulate the major transcription factor NFκB in endothelial cells which induces pro-inflammatory cytokine production and inhibits endothelial cell apoptosis.
Host defense and immunity
Initial innate immune responses to Rickettsia involve activation of natural killer cells by activated dendritic cells following engulfment of bacteria. They produce large quantities of IL-12 that stimulate natural killer (NK) cells to produce INF-γ. Therefore during the early stages of infection, there are increased numbers of NK cells. The pro-inflammatory cytokines IFN-γ, TNF-α, IL-1β and IL-6 cause fever and increased vascular permeability which causes a maculopapular rash with non-blanching petechiae. The cytokines also activate the infected endothelial cells to kill Rickettsiae via two autophagic mechanisms – nitric oxide and hydrogen peroxide.