Establishment of mouse models with pulmonary infection by liquid aerosol-exposure Brucella and toxicology evaluation

WEI Chao; YANG Wen-hui; ZHOU Dong-sheng; Yang Hui-ying; SUN Li-na; FAN Wei-ping; LI Zhen-jun

doi:10.3969/j.issn.1007-8134.2018.03.012

Abstract：Objective To establish mouse models with pulmonary infection due to exposure to liquid aerosol of Brucella and assess its toxicological effects. Methods BALB/c female mice of 6 to 8 weeks old were exposed to Brucella abortus strain S19-CN (S19-CN) by intra-tracheal aerosol delivery route or intranasal instillation route. At 0, 2, 4, 6, 8 weeks post-infection, clinical signs were observed and recorded. Specimens were harvested to count bacteria burdens in lungs and spleens. The specific antibodies in serum and the cytokines in serum or lung homogenate were detected. Results Compared with the blank control group, no significant clinical sign or body weight decrease was found in mice of intra-tracheal aerosol delivery route group and intranasal instillation route group after infection. The spleen weight reached the peak at the second week and the fourth week post-infection respectively. The bacteria burdens in lung reached the peak at the second week, approximate to 107CFU/g; serum antibody maintained a high level within 8 weeks post-infection; High-concentration cytokines IFN-γ and TNF-α were detectable in serum and lung homogenate of rats in both intra-tracheal aerosol delivery route group and intranasal instillation route group, and the former was higher than the latter. The difference was statistical compared with blank control group (P ＜ 0.05). Conclusions Mouse model with pulmonary infection due to exposure to liquid aerosol of Brucella has been established successfully by intra-tracheal delivery of liquid aerosol of Brucella S19-CN in BALB/c mice. S19-CN causes chronic infection of BALB/c mice, induces significant splenomegaly and produces significant toxicological effects. Meanwhile, it elicits significant cellular and humoral immune response.