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 limit contact with contagious individuals. Gram-negative bacteria produce exopolysaccharide (EPS) that provides microbial protection; however, the impact of EPS on sickness remains uncertain. 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 hypothermia mediated by TLR4 detection of the exposed lipopolysaccharide (LPS) in lung TRPV1+ sensory neurons. However, inflammation did not account for sickness. Stimulation of lung nociceptors induced acute stress responses in the paraventricular hypothalamic nuclei by activating corticotropin-releasing hormone neurons responsible for sickness behavior and hypothermia. Thus, EPS-producing biofilm pathogens evade initiating a lung-brain sensory neuronal response that results in sickness.
摘要：
肺部感染引起可观察到的疾病，被认为是继发于炎症。疾病的迹象对于通过行为免疫反应提醒他人以限制与传染性个体的接触至关重要。革兰氏阴性菌产生胞外多糖（EPS），提供微生物保护;然而，EPS对疾病的影响仍不确定。使用基因组工程的铜绿假单胞菌（P.铜绿假单胞菌)菌株，我们比较了EPS生产者与非生产者和一种毒性大肠杆菌(E.coli)雄性和雌性小鼠肺部感染模型。EPS阴性铜绿假单胞菌和毒性大肠杆菌感染引起严重疾病，行为改变，炎症,和低温介导的TLR4检测肺TRPV1+感觉神经元中暴露的脂多糖(LPS)。然而,炎症不是疾病的原因。通过激活负责疾病行为和体温过低的促肾上腺皮质激素释放激素神经元，刺激肺伤害感受器在下丘脑室旁核中引起急性应激反应。因此，产生EPS的生物膜病原体逃避启动导致疾病的肺-脑感觉神经元反应。
