{Reference Type}: Journal Article
{Title}: Biofilm exopolysaccharides alter sensory-neuron-mediated sickness during lung infection.
{Author}: Granton E;Brown L;Defaye M;Moazen P;Almblad H;Randall TE;Rich JD;Geppert A;Abdullah NS;Hassanabad MF;Hiroki CH;Farias R;Nguyen AP;Schubert C;Lou Y;Andonegui G;Iftinca M;Raju D;Vargas MA;Howell PL;Füzesi T;Bains J;Kurrasch D;Harrison JJ;Altier C;Yipp BG;
{Journal}: Cell
{Volume}: 187
{Issue}: 8
{Year}: 2024 Apr 11
{Factor}: 66.85
{DOI}: 10.1016/j.cell.2024.03.001
{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.