近日，加拿大卡尔加里大学Bryan G. Yipp等研究人员合作发现，生物膜外多糖改变肺部感染期间感觉神经元介导的疾病。相关论文于2024年3月21日在线发表在《细胞》杂志上。
研究人员利用基因组工程铜绿假单胞菌（P. aeruginosa）菌株，比较了外多糖（EPS）产生者和非产生者，以及雌雄小鼠的毒性大肠杆菌（E. coli）肺部感染模型。EPS阴性的铜绿假单胞菌和毒性大肠杆菌感染会导致严重的疾病、行为改变、炎症和低体温，这些都是由肺部TRPV1+感觉神经元中暴露的脂多糖（LPS）的TLR4检测所介导的。
然而，炎症并不是疾病的原因。肺部痛觉感受器受到刺激后，会激活下丘脑室旁核的促肾上腺皮质激素释放激素神经元，从而诱发急性应激反应，导致生病行为和低体温。因此，产生EPS的生物膜病原体会逃避启动肺-脑感觉神经元反应，从而导致生病。
据悉，肺部感染会引起可观察到的疾病，这被认为是继发于炎症。生病的迹象对于通过行为免疫反应提醒他人限制与传染者的接触至关重要。革兰氏阴性细菌产生的EPS可提供微生物保护，然而，EPS对疾病的影响仍不确定。
附：英文原文
Title: Biofilm exopolysaccharides alter sensory-neuron-mediated sickness during lung infection
Author: Elise Granton, Luke Brown, Manon Defaye, Parisa Moazen, Henrik Almblad, Trevor E. Randall, Jacquelyn D. Rich, Andrew Geppert, Nasser S. Abdullah, Mortaza F. Hassanabad, Carlos H. Hiroki, Raquel Farias, Angela P. Nguyen, Courtney Schubert, Yuefei Lou, Graciela Andonegui, Mircea Iftinca, Deepa Raju, Mario A. Vargas, P. Lynne Howell, Tamás Füzesi, Jaideep Bains, Deborah Kurrasch, Joe Jonathan Harrison, Christophe Altier, Bryan G. Yipp
Issue&Volume: 2024-03-21
Abstract: Infections of the lung cause observable sickness thought to be secondary to inflammation.Signs of sickness are crucial to alert others via behavioral-immune responses to limitcontact with contagious individuals. Gram-negative bacteria produce exopolysaccharide(EPS) that provides microbial protection; however, the impact of EPS on sickness remainsuncertain. Using genome-engineered Pseudomonas aeruginosa (P. aeruginosa) strains, we compared EPS-producers versus non-producers and a virulent Escherichia coli (E. coli) lung infection model in male and female mice. EPS-negative P. aeruginosa and virulent E. coli infection caused severe sickness, behavioral alterations, inflammation, and hypothermiamediated by TLR4 detection of the exposed lipopolysaccharide (LPS) in lung TRPV1+ sensory neurons. However, inflammation did not account for sickness. Stimulationof lung nociceptors induced acute stress responses in the paraventricular hypothalamicnuclei by activating corticotropin-releasing hormone neurons responsible for sicknessbehavior and hypothermia. Thus, EPS-producing biofilm pathogens evade initiating alung-brain sensory neuronal response that results in sickness.
DOI: 10.1016/j.cell.2024.03.001
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00249-6