Vaccination induces rapid protection against bacterial pneumonia via training alveolar macrophage in mice

eLife

Yuan Zhuang¹  Quanming Zou¹  Hao Zeng¹  Jinyong Zhang¹  Liusheng Peng¹  Jiang Gu¹  Weijun Zhang¹  Haibo Li¹  Xi Zeng²  Gang Guo³  Yangyang Zhou³  Yan Li³  Chuanying Xiang³  Ning Wang³  Kaiyun Liu³  Xiaomin Zhang³  Yun Shi³  Jixin Zhang³  Hao Gu⁴ 

[1] National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China;National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China;Department of Phamacy, The 78 th Group Army Hospital of Chinese People's Liberation Army, Mudanjiang, China;West China Biopharmaceutical Research Institute,West China Hospital, Sichuan University, Chengdu, China;West China Biopharmaceutical Research Institute,West China Hospital, Sichuan University, Chengdu, China;National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China;Department of Clinical Laboratory, 971st Hospital of People's Liberation Army, Qingdao, China;

关键词: multidrug-resistant bacteria;    vaccine;    alveolar macrophage;    Trained immunity;    Acinetobacter baumannii;    rapid effect;    Multidrug-resistant bacteria;    Vaccine;    Rapid effect;    Alveolar macrophage;    Trained immunity;    Acinetobacter baumannii;    Pseudomonas aeruginosa;    Klebsiella pneumoniae;   

DOI  :  10.7554/eLife.69951

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Vaccination strategies for rapid protection against multidrug-resistant bacterial infection are very important, especially for hospitalized patients who have high risk of exposure to these bacteria. However, few such vaccination strategies exist due to a shortage of knowledge supporting their rapid effect. Here, we demonstrated that a single intranasal immunization of inactivated whole cell of Acinetobacter baumannii elicits rapid protection against broad A. baumannii-infected pneumonia via training of innate immune response in Rag1-/- mice. Immunization-trained alveolar macrophages (AMs) showed enhanced TNF-α production upon restimulation. Adoptive transfer of immunization-trained AMs into naive mice mediated rapid protection against infection. Elevated TLR4 expression on vaccination-trained AMs contributed to rapid protection. Moreover, immunization-induced rapid protection was also seen in Pseudomonas aeruginosa and Klebsiella pneumoniae pneumonia models, but not in Staphylococcus aureus and Streptococcus pneumoniae model. Our data reveal that a single intranasal immunization induces rapid and efficient protection against certain Gram-negative bacterial pneumonia via training AMs response, which highlights the importance and the possibility of harnessing trained immunity of AMs to design rapid-effecting vaccine.

【 授权许可】

CC BY