Exploratory study on pathogenesis of far-eastern spotted fever

Abstract

Far-eastern spotted fever is an emerging disease caused by Rickettsia heilongjiangensis, a tick-borne obligate intracellular bacterium. In this study, R. heilongjiangensis was used to infect BALB/c mice by inoculation of retro-orbital venous plexus to imitate a blood infection caused by tick biting. We found that R. heilongjiangensis rapidly entered the circulation for systemic dissemination and the pathogen existed in liver, spleen, lungs, and brain of the mice at least 9 days post-infection (p.i.). Severe pathological lesions were observed in liver, lungs, and brain at Day 6 p.i. In addition, the elevated levels of inflammatory cytokines, including interferon-γ, tumor necrosis factor, and CC chemokine, were detected in the infected organs at Day 3 p.i. Our results reveal that R. heilongjiangensis may cause an infection in BALB/c mice and the pathological lesions in the infected mice are associated with host inflammatory response induced by R. heilongjiangensis.

Figure 1.

Rickettsial loads in blood and organs of R. heilongjiangensis-infected mice.

Figure 2.

Pathological lesions in R. heilongjiangensis-infected mice. The tissue samples of the organs were obtained from the R. heilongjiangensis-infected mice at Day 6 p.i. Perivascular infiltration of inflammatory cells and swelling of liver cells were observed in the liver of mice infected with viable R. heilongjiangensis (A and B, original magnifications ×400). Lung lesion consisting of perivascular inflammatory infiltration and alveolar interstitial thickening are observed (C and D, original magnifications ×200). Microhemorrhage was found in the brain (E and F, original magnifications ×100).

Figure 3.

Specific antibody responses in the mice after R. heilongjiangensis infection.

Figure 4.

Messenger RNA (mRNA) expression of interferon-gamma (IFN-γ), tumor necrosis factor (TNF), and RANTES in tissues of mice infected with R. heilongjiangensis. V, depicts that mice were inoculated with viable organisms; I, depicts that mice were inoculated with inactivated organisms.