title: Mouse Model of Coxiella burnetii Aerosolization.
abstract: Coxiella burnetii is mainly transmitted by aerosols and is responsible for multiple-organ lesions. Animal models have shown C. burnetii pathogenicity, but long-term outcomes still need to be clarified. We used a whole-body aerosol inhalation exposure system to mimic the natural route of infection in immunocompetent (BALB/c) and severe combined immunodeficient (SCID) mice. After an initial lung inoculum of 10(4) C. burnetii cells/lung, the outcome, serological response, hematological disorders, and deep organ lesions were described up to 3 months postinfection. C. burnetii-specific PCR, anti-C. burnetii immunohistochemistry, and fluorescent in situ hybridization (FISH) targeting C. burnetii-specific 16S rRNA completed the detection of the bacterium in the tissues. In BALB/c mice, a thrombocytopenia and lymphopenia were first observed, prior to evidence of C. burnetii replication. In all SCID mouse organs, DNA copies increased to higher levels over time than in BALB/c ones. Clinical signs of discomfort appeared in SCID mice, so follow-up had to be shortened to 2 months in this group. At this stage, all animals presented bone, cervical, and heart lesions. The presence of C. burnetii could be attested in situ for all organs sampled using immunohistochemistry and FISH. This mouse model described C. burnetii Nine Mile strain spread using aerosolization in a way that corroborates the pathogenicity of Q fever described in humans and completes previously published data in mouse models. C. burnetii infection occurring after aerosolization in mice thus seems to be a useful tool to compare the pathogenicity of different strains of C. burnetii.
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.|Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Centre Hospitalo-Universitaire Timone, Assistance Publique des Hôpitaux de Marseille, Marseille, France.
authors.forename: Cléa
authors.initials: C
authors.lastname: Melenotte
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Lepidi
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Nappez
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
authors.forename: Yassina
authors.initials: Y
authors.lastname: Bechah
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Audoly
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Terras
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France.|Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Centre Hospitalo-Universitaire Timone, Assistance Publique des Hôpitaux de Marseille, Marseille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, Marseille, France fabienne.bregeon@ap-hm.fr.|Service des Explorations Fonctionnelles Respiratoires Centre Hospitalo-Universitaire Nord, Pôle Cardio-Vasculaire et Thoracique, Assistance Publique Hôpitaux de Marseille, Marseille, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Brégeon
mesh_terms: D000336:Aerosols; D000818:Animals; D001772:Blood Cell Count; D016997:Coxiella burnetii / Q000235:genetics; D004195:Disease Models, Animal; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010641:Phenotype; D011778:Q Fever / Q000175:diagnosis / Q000382:microbiology* / Q000635:transmission*
chemical_list: D000336:Aerosols