TLR-2-mediated activation of innate responses in the upper airways confers anti-viral protection of the lungs

The impact of respiratory virus infections on global health is felt not just during a pandemic but for many, endemic seasonal infections pose an equal and ongoing risk of severe disease. Moreover, vaccines and antiviral drugs are not always effective or available for many respiratory viruses. We investigated how induction of effective and appropriate antigen independent innate immunity in the upper airways can prevent spread of respiratory virus infection to the vulnerable lower airways. Activation of Toll-like receptor-2 (TLR2), when restricted to the nasal turbinates results in prompt induction of innate immune-driven anti-viral responses through action of cytokines, chemokines and cellular activity in the upper but not the lower airways. We define how nasal epithelial cells and recruitment of macrophages work in concert and play pivotal roles to limit progression of influenza virus to the lungs and sustain protection for up to seven days. These results reveal underlying mechanisms of how control of viral infection in the upper airways can occur and also support the implementation of strategies that can activate TLR2 in nasal passages to provide rapid protection, especially for at-risk populations, against severe respiratory infection when vaccines and antiviral drugs are not always effective or available.