State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20(#) Dong-Dia-Jie Street, Fengtai, Beijing 100071, China.
Anhui Medical University, Mei-Shan Road, Hefei, Anhui 230032, China.
Vaccine. 2019 Sep 24;37(41):6076-6084. doi: 10.1016/j.vaccine.2019.08.041. Epub 2019 Aug 30.
Human Q fever is recognized as a worldwide public health problem. It often occurs by inhalation of airborne aerosols contaminated with Coxiella burnetii, a gram-negative intracellular bacterium, mainly from domestic livestock. In this study, we analyzed the possibility to establish mucosal and systemic immunity against C. burnetii infection using a pulmonary delivery of chloroform-methanol residue of C. burnetii (CMR) vaccine. Mice were immunized by the intratracheal inoculation of CMR (IT-CMR) or the subcutaneous injection of CMR (SC-CMR), and the immunized mice were challenged with C. burnetii by the intratracheal route. The levels of IFN-γ, IL-12p70, IL-5, and IL-4 in the IT-CMR group in splenic T cells stimulated ex vivo were significantly higher than in the SC-CMR group. Significantly elevated sIgA to C. burnetii was detected in the bronchoalveolar lavage fluid of mice immunized by IT-CMR but not by SC-CMR, which might have contributed to the significant reduction in C. burnetii load and pathological lesions in the lungs of the mice after the challenge of C. burnetii. These results suggest that compared with SC-CMR in mice, IT-CMR was more efficient to elicit cellular and lung mucosal immune responses against aerosol infection of C. burnetii.
人 Q 热被认为是一个全球性的公共卫生问题。它通常通过吸入被柯克斯体污染的空气传播,柯克斯体是一种革兰氏阴性细胞内细菌,主要来自家畜。在这项研究中,我们分析了使用氯仿-甲醇残渣(CMR)疫苗经肺递送来建立针对 C. burnetii 感染的粘膜和全身免疫的可能性。通过气管内接种 CMR(IT-CMR)或皮下注射 CMR(SC-CMR)对小鼠进行免疫,并用气管内途径用 C. burnetii 对免疫小鼠进行攻毒。在体外刺激脾 T 细胞中,IT-CMR 组的 IFN-γ、IL-12p70、IL-5 和 IL-4 水平明显高于 SC-CMR 组。在 IT-CMR 免疫的小鼠的支气管肺泡灌洗液中检测到针对 C. burnetii 的显著升高的 sIgA,但在 SC-CMR 免疫的小鼠中没有检测到,这可能有助于在 C. burnetii 攻毒后减少 C. burnetii 负荷和肺部的病理损伤。这些结果表明,与 SC-CMR 相比,IT-CMR 更有效地诱导细胞和肺部粘膜免疫反应,以抵抗 C. burnetii 的气溶胶感染。