Respiratory infections of the upper and lower airways trigger a range of symptoms, including altered breathing, social disengagement, malaise and lethargy, which result from the systemic inflammatory response to infection. Various microorganisms can lead to respiratory infections. An example is the Gram-negative bacterium Pseudomonas aeruginosa, which can cause both acute and chronic lung infections. Typically, P. aeruginosa resides within biofilms that pose a challenge for treatment, as they protect the bacteria from antibiotics and the host immune response. P. aeruginosa biofilms are formed mainly by exopolysaccharide (EPS) molecules like Pel and Psl. The impact of EPS on host immunity and disease in vivo remains unknown. In this study, Granton et al. link the symptoms and behavioural changes presented during P. aeruginosa lung infection with biofilm formation, showing that biofilm-associated EPS controls sickness.

Next, the authors hypothesized that EPS could help bacteria evade host detection of lipopolysaccharide (LPS), a major pathogen-associated molecular pattern of Gram-negative bacteria that binds to host Toll-like receptor 4 (TLR4). Indeed, by infecting Tlr4–/– mice with P. aeruginosa EPS+ and EPS– strains, the researchers demonstrated that EPS molecules hide LPS from being recognized by TLR4 during P. aeruginosa infection, resulting in impaired clinical sickness. This was also evidenced by attenuated sickness and hypothermia in TLR4-deficient mice infected with the EPS– strain.