Intranasal exposure to commensal bacterium Rothia mucilaginosa protects against influenza A virus infection

The respiratory tract hosts a diverse microbial community whose composition varies with anatomical location and throughout life. Rothia mucilaginosa , a common commensal of the upper respiratory tract and oral cavity, has recently been recognized for its ability to inhibit bacteria-triggered pro-inflammatory responses. However, its role in modulating the immune response to viral infections such as influenza A virus (IAV) pneumonia, remains unknown. Here, we demonstrate that R. mucilaginosa enhances protection against IAV, promoting viral clearance, reducing inflammation, preserving bronchial and alveolar structures, and improving survival in a mouse model of influenza pneumonia. The enhanced viral clearance observed in R. mucilaginosa -treated mice is associated with the recruitment of innate immune cells to the lungs, including PD-L1-expressing neutrophils, alongside the production of the anti-inflammatory cytokine IL-10, both of which are known to play regulatory roles in the context of IAV infection. Together, these findings highlight R. mucilaginosa -mediated innate immune priming as a key protective mechanism in the respiratory tract against IAV infection. • R. mucilaginosa exposure triggers a rapid and transient immune response in mice. • Pre-exposure to R. mucilaginosa enhances survival and viral clearance in IAV-infected mice. • It also reduces lung inflammation and epithelial damage in IAV-infected mice.