%0 Journal Article
%T Biofilm exopolysaccharides alter sensory-neuron-mediated sickness during lung infection.
%A Granton E
%A Brown L
%A Defaye M
%A Moazen P
%A Almblad H
%A Randall TE
%A Rich JD
%A Geppert A
%A Abdullah NS
%A Hassanabad MF
%A Hiroki CH
%A Farias R
%A Nguyen AP
%A Schubert C
%A Lou Y
%A Andonegui G
%A Iftinca M
%A Raju D
%A Vargas MA
%A Howell PL
%A Füzesi T
%A Bains J
%A Kurrasch D
%A Harrison JJ
%A Altier C
%A Yipp BG
%J Cell
%V 187
%N 8
%D 2024 Apr 11
%M 38518773
%F 66.85
%R 10.1016/j.cell.2024.03.001
%X 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.