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.

Coxiella burnetiiIsolates Cause Genogroup-Specific Virulence in Mouse and Guinea Pig Models of Acute Q Fever

“…The ID 50 was determined by detecting seroconversion (immunoglobulin G [IgG], Ͼ1:16) using indirect microimmunofluorescence. The LD 50 was determined as reported previously (1).…”

“…To quantify the growth of C. burnetii, DNA was extracted from spleen tissue and C. burnetii com1 gene copies were detected by qPCR as previously described (8). The heart, lung, liver, spleen, kidney, and femur were formalin fixed, embedded in paraffin, sliced, and then prepared by hematoxylin-eosin staining and immunocytochemistry, as described previously (1,8), to evaluate histopathologic changes and bacterial distribution in tissues. The degree of inflammation present in each tissue sample was scored numerically by the following system: 0, none; 1, mild; 2, moderate; 3, marked; 4, severe.…”

“…We speculated that with these highly sensitive rodent models it may be possible to observe intra-and intergroup pathogenicity differences of C. burnetii isolates. To confirm whether SCID mice could be used to model isolate-specific virulence, we gave multiple infectious doses of a group IV Q fever isolate to immune-competent CB-17 and SCID mice (on the same background) to compare them with previously reported group I isolate (NM) infections (1). Eight isolates from four genomic groups (Table 1) were then evaluated for the ability to cause acute disease in SCID mouse i.p.-challenge and guinea pig aerosol challenge models.…”

Comparison of Japanese Isolates of Coxiella burnetii by PCR‐RFLP and Sequence Analysis

“…Much can be learned about antigenicity and pathogenicity of the Japanese isolates by using monoclonal antibodies (8,9) and a new animal model for Q fever which has been reported previously (2). Additional studies of the antigenicity and pathogenicity of Japanese isolates can reveal not only the character of the Japanese isolates of C. burnetii, but also the practicality of PCR-RFLP of the icd gene for the typing of C. burnetii isolates.…”

In Vitro Susceptibility to Tetracycline and Fluoroquinolones of Japanese Isolates of Coxiella burnetii

“…However, as we described previously, a successful mouse model for Q fever endocarditis was established (2). This SCID mouse model may make it possible to evaluate the in vivo antibiotic susceptibility of C. burnetii.…”