Department of Microbiology, Miami University, Oxford, Ohio, USA.
J Infect Dis. 2023 Aug 11;228(3):353-363. doi: 10.1093/infdis/jiad069.
Acinetobacter baumannii causes a wide range of dangerous infections due to the emergence of pandrug-resistant strains. Therefore, there is a need for alternative therapeutics to treat these infections, including those targeting the host immune responses. However, immune responses, especially the humoral response against this pathogen, are poorly understood.
This study investigated the lymphocyte-mediated innate immune resistance to A. baumannii AB5075 pulmonary infection using B- and T-cell-deficient (Rag2-/-) mice, the protective effect of natural antibodies (NAbs), and the expression of complement-mediated responses using a mouse pneumonia model.
Our results showed that intranasally infected Rag2-/- mice are impaired in clearing bacteria from lung, liver, and spleen at 24 hours postinfection compared to wildtype mice. Animal pretreatment with normal mouse serum or purified antibodies from naive mice rescued Rag2-/- mice from infection. Analysis of C3 complement protein binding demonstrated that NAbs increased C3 protein deposition on A. baumannii cells, indicating the activation of the classical complement pathway by NAbs.
Overall, our study shows that NAbs mediate innate immune resistance against A. baumannii, a finding that may lead to the development of effective therapies against human infections caused by this antibiotic-resistant A. baumannii.
由于泛耐药菌株的出现，鲍曼不动杆菌引起了广泛的危险感染。因此，需要替代疗法来治疗这些感染，包括针对宿主免疫反应的治疗方法。然而，免疫反应，特别是针对这种病原体的体液反应，还了解甚少。
本研究使用 B 细胞和 T 细胞缺陷（Rag2-/-）小鼠，研究了淋巴细胞介导的对 AB5075 型鲍曼不动杆菌肺部感染的固有免疫抵抗作用，天然抗体（NAbs）的保护作用，以及使用小鼠肺炎模型对补体介导反应的表达。
我们的结果表明，与野生型小鼠相比，在感染后 24 小时，经鼻腔感染的 Rag2-/-小鼠肺部、肝脏和脾脏的细菌清除能力受损。用正常小鼠血清或来自未感染小鼠的纯化抗体预处理动物，可使 Rag2-/-小鼠免受感染。对 C3 补体蛋白结合的分析表明，NAbs 增加了 A. baumannii 细胞上 C3 蛋白的沉积，表明 NAbs 激活了经典的补体途径。
总的来说，我们的研究表明，NAbs 介导了对鲍曼不动杆菌的固有免疫抵抗，这一发现可能导致针对这种抗生素耐药的鲍曼不动杆菌引起的人类感染的有效治疗方法的发展。
