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.

肺部感染会引起明显的疾病，被认为是继发于炎症的。疾病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。革兰氏阴性细菌产生胞外多糖（EPS），提供微生物保护；然而，EPS 对疾病的影响仍不确定。使用基因组工程铜绿假单胞菌( P. aeruginosa ) 菌株，我们比较了 EPS 生产者与非生产者以及雄性和雌性小鼠的强毒力大肠杆菌( E. coli ) 肺部感染模型。 EPS 阴性铜绿假单胞菌和强毒力大肠杆菌感染导致严重疾病、行为改变、炎症和体温过低，这些症状是由肺 TRPV1 ⁺感觉神经元中暴露的脂多糖 (LPS) 的 TLR4 检测介导的。然而，炎症并不能解释疾病。刺激肺部伤害感受器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，诱导室旁下丘脑核团的急性应激反应。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，从而导致疾病。