Pseudomonas aeruginosa exotoxin A as a novel allergen induced Non-TH2 inflammation in a murine model of steroid-insensitive asthma

作者：Huancheng Xie, Linmei Li, Yuhe Guo, Linghui Zhou, Linyi Ma, Andong He, He Lai, Ying He, Yongping Liu, Huifang Chen, Liping Luo, Yuyi Huang, Xiaokang Sha, Huanping Zhang, Jie Yan, Qingling Zhang, Ailin Tao · 发表于：Heliyon · 年份：2024 · DOI：10.1016/j.heliyon.2024.e37512 · 被引用次数：3 · 研究领域：Toxin Mechanisms and Immunotoxins、Bacterial biofilms and quorum sensing、Asthma and respiratory diseases

Background Despite the immediate in vivo occurrence of anaphylactic and allergic reactions following treatment with Pseudomonas aeruginosa exotoxin A (PEA)-based immunotoxins, the immunological role of PEA in asthma pathogenesis remains unclear. Objective This study investigated the allergenic potential of PEA and the specific type of asthma induced. Methods Recombinant PEA (rPEA) lacking domain Ia (to eliminate non-specific cytotoxicity) was expressed, purified, and employed to detect serum PEA-specific IgE levels in asthmatic patients. Competitive ELISA assays were used to assess rPEA's IgE binding capacity and allergenicity. Additionally, rPEA-challenged C57BL/6 mice were subjected to inflammatory endotyping and therapeutic assays to characterize the allergic nature of PEA. Results PEA-specific IgE was identified in 17 (14.2 %) of 120 asthma patients. The rPEA-sensitized and challenged mice had increased PEA-specific immunoglobulins (such as IgE, IgG1 and IgG2a) and developed asthma-like phenotypes with airway hyperresponsiveness, severe airway inflammation, and airway remodeling. Lungs from these mice displayed significant increases in neutrophils and IL-17A + cells. Innate lymphoid cells (ILCs) produced type 2 cytokines (IL-4, IL-5, and IL-13), whereas Th cells did not. Nonetheless, airway inflammation, rather than hyperresponsiveness, was elicited in non-sensitized mice upon challenge with rPEA. Importantly, rPEA-induced asthmatic mice were unresponsive to dexamethasone...