Innate immunity to influenza virus: implications for future therapy

Abstract

Innate immunity is critical in the early containment of influenza virus infection. The innate response is surprisingly complex. A variety of soluble innate inhibitors in respiratory secretions provide an initial barrier to infection. Dendritic cells, phagocytes and natural killer cells mediate viral clearance and promote further innate and adaptive responses. Toll-like receptors 3 and 7 and cytoplasmic RNA sensors are critical for activating these responses. In general, the innate response restricts viral replication without injuring the lung; however, the 1918 pandemic and H5N1 strains cause more profound, possibly harmful, innate responses. In this review, we discuss the implications of burgeoning knowledge of innate immunity for therapy of influenza.

Figure 1. Diagram of the neck and carbohydrate recognition domains of SP-D

This ribbon diagram was derived from x-ray crystallographic studies of the trimeric binding domain of SP-D in association with the coiled coil neck domain, which is responsible for trimerization. Three saccharide-binding pockets are located on the flat upper surface of the trimer (see spherical single green calcium ion in the pocket). The binding pocket is surrounded on either side by ridges, and substitution of the R343 residue that forms one of the ridges can greatly increase influenza viral-neutralizing activity. Insertions of amino acids (e.g., RAK or AAA, as shown) adjacent to the other ridge also increases antiviral activity to a lesser extent. The location of the N-linked sialylated glycan on pig SP-D is also shown. SP: Surfactant protein.