Induction of a proinflammatory response is the hallmark of host innate defense against invading pathogens. Host recognition of influenza A virus (IAV) infection relies on pattern-recognition receptors, including Toll-like receptor 7 (TLR7) and retinoic acid inducible gene-1 (RIG-I) for the activation of innate-immune responses. Here, we show that following a physiological low dose of IAV infection, viral sensing by either TLR7 or RIG-I induces a proinflammatory program that promotes viral replication. Transfer of bronchoalveolar lavage from infected wild-type mice into the airway of mice deficient in TLR7 and RIG-I pathways was sufficient to restore viral replication efficiency. Comparison of IAV-infected cells revealed that inflammatory mediators elicited by TLR7 and RIG-I signaling recruit viral target cells to the airway, thereby enhancing viral load within the respiratory tract. Our data suggest that IAV uses physiological levels of inflammatory responses for its replicative advantage and highlight the complex interplay between viruses and the host innate-immune responses.
Keywords: cytokine; inflammation; monocytes.