SCID mouse model for lethal Q fever

Abstract

Q fever, a worldwide zoonosis caused by Coxiella burnetii, has many manifestations in humans. Endocarditis is the most serious complication of Q fever. Animal models are limited to acute pulmonary or hepatic disease and reproductive disorders. An appropriate experimental animal model for Q fever endocarditis does not yet exist. In this study, severe combined immunodeficient (SCID) mice infected with C. burnetii showed persistent clinical symptoms and died, whereas immunocompetent mice similarly infected became asymptomatic and survived. The SCID mice examined in this study had severe chronic lesions in their primary organs: the heart, lung, spleen, liver, and kidney. The heart lesions of the SCID mice were similar to those in humans with chronic Q fever endocarditis: they had focal calcification and expanded macrophages containing C. burnetii. The 50% lethal dose of C. burnetii in SCID mice was at least 10(8) times less than that in immunocompetent mice. The SCID mouse is highly susceptible to C. burnetii, and the immunodeficiency of the host enhances the severity of Q fever. This animal model could provide a new tool for the study of chronic Q fever and Q fever in immunodeficient hosts.

FIG. 1.

Weight changes of SCID mice inoculated with C. burnetii (solid circles) and PBS (open circles). A significant difference (P < 0.005) between infected and control mice was found 10 days p.i. Relative body weight is the body weight on a particular day divided by the body weight on the day of inoculation. Points represent means, error bars indicate standard deviations, and † indicates death of the mouse.

FIG.2.

Heart (A and B) and kidney (C) sections from SCID mouse infected with C. burnetii. (A) Calcifications were observed in severely infiltrated lesions (arrows). There was macrophage infiltration in the epicardium (EP) and myocardium (MC). The macrophages were expanded and packed with granules (arrowheads). Hematoxylin and eosin staining; magnification, ×200. (B) C. burnetii antigens were detected as brown granules (arrowheads). ABC method; magnification, ×400. EN, endocardium; V, ventricle. (C) C. burnetii antigen-positive cells were characteristic in glomeruli (arrowheads). ABC method; magnification, ×200.

FIG.3.

Immunocytochemistry of the lung (top), liver (middle), and spleen (bottom) of SCID mouse infected with C. burnetii. C. burnetii antigens were detected as brown granules. (Top) C. burnetii antigen-positive cells infiltrated particularly in the stroma adjacent to a bronchiole (BR). AL, alveolus. (Middle) C. burnetii antigens were also found in hepatocytes (arrowheads). (Middle and bottom) The margins of vacuoles were immunopositive (arrows). ABC method; magnification, ×200.