Innate Immunity to Influenza A Virus Infection

Influenza A virus poses particular problems in host defense due to its ability to vary antigenic properties. Innate immunity is most critical during the early phase of IAV infection prior to elaboration of adaptive immune responses. Recent research highlights the importance of pulmonary surfactant collectins (especially surfactant protein D or SP-D) in both restricting the extent of viral replication and limiting potentially damaging inflammation in the first few days of IAV infection. Other innate inhibitors of importance for host defense against IAV include type I IFNs and alveolar macrophages. Recent studies also highlight the role of Toll-like receptors (TLRs) 3 and 7, plasmacytoid dendritic cells, and natural killer (NK) cells. Soluble scavenger receptor rich glycoprotein 340 (gp-340) and defensins also have anti-IAV activity. Neutrophils also contribute in complex ways to host response to IAV, and increased neutrophil influx characterizes severe IAV infection in which the usual innate responses are ineffective. Some innate mechanisms strongly affect elaboration and intensity of the adaptive immune response to IAV. A key conclusion of this review is that the innate immune system not only plays a role in non-specific restriction of viral replication, but also in down regulating non-specific and antigen specific immune injury. Excessive inflammatory responses are now implicated in many severe outcomes of IAV infection. Better understanding of innate immunity to IAV should clarify why some subjects are at greater risk for severe IAV infection, and why certain IAV strains are more virulent, and also suggest novel anti-viral and anti-inflammatory therapeutic approaches.