Abstract
Q fever is a worldwide zoonosis caused by Coxiella burnetii. Human Q fever is typically acquired through inhalation of contaminated aerosols, resulting in an initial pulmonary infection. In this study, BALB/c mice were infected with C. burnetii via an intratracheal (IT) route using a non-invasive aerosol pulmonary delivery device to directly place the living C. burnetii organisms into the lungs of the mice. The bacterial loads, pathological lesions, and antibody and cellular responses were analyzed and compared with those of mice infected via an intraperitoneal (IP) route. Compared with mice infected via an IP route, mice infected via an IT route exhibited a higher bacterial load and more severe pathological lesions in the heart and lungs at days 3 and 7 post-infection (pi). The levels of interferon-γ and IL-12p70 in the serum of mice infected via the IT route were significantly higher than those of mice infected via the IP route at day 3 pi. In conclusion, this murine model of acute C. burnetii infection via IT inoculation closely resembles the natural route of C. burnetii infection than that of IP injection. Thus, this newly developed model will be useful for investigating the pathogenesis and immunity of C. burnetii aerosol infection, as well as for the evaluation of therapeutic drugs and preventive vaccines of Q fever.
Highlights
Q fever is a worldwide zoonosis caused by Coxiella burnetii, an intracellular Gram-negative bacterium
Animal models of acute C. burnetii infection, which simulate the natural route of infection and clinical presentations associated with human acute Q fever, have been developed in guinea pigs, mice, and non-human primates
The results in the present study confirm that a BALB/c murine model of acute C. burnetii infection was successfully established via IT inoculation with C. burnetii using a non-invasive aerosol pulmonary delivery device
Summary
Q fever is a worldwide zoonosis caused by Coxiella burnetii, an intracellular Gram-negative bacterium. C. burnetii infection exhibits various acute and chronic clinical manifestations in humans. Acute Q fever is generally a flu-like illness with a high fever, headache, malaise, and myalgia [1], while chronic Q fever frequently presents as endocarditis [2], and/or hepatitis [3], and occasionally appears as osteomyelitis [4]. Pathologic changes and immune responses against Coxiella burnetii infection in mice
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