Tau is necessary for Pseudomonas aeruginosa-induced blood-brain barrier dysfunction

Many patients suffer from incident dementia after lung infections. Previous studies demonstrated that cytotoxic tau is released from the lungs in response to bacterial pneumonia, causing cognitive deficits and tau seeding. We aimed to determine the impact pneumonia has on blood-brain barrier (BBB) permeability, glial activation, and tau phosphorylation in the brain following infection and the involvement of tau. We found that lung infection with Pseudomonas aeruginosa (P. aeruginosa) increased BBB permeability, astrocyte activation, and phosphorylated tau (ptau) levels in the brain 24-hours (h) post-infection in C57BL/6J mice. Conversely, tau knockout (KO) mice had no BBB injury or glial activation 24 h after infection. Additionally, we found increased levels of several kinases and proinflammatory cytokines with infection in C57BL/6J and tau KO mice. Thus, tau is necessary for pneumonia-induced BBB dysfunction and astrocyte reactivity in the brain and may be an innate immune response link between infection and dementia. Pre-clinical models of bacterial pneumonia reveal an important role of tau in systemic infections. Pneumonia causes AD-like tau phosphorylation in the brain. Additionally, tau is required for pneumonia-induced neurovascular dysfunction.