Structured regulation of inflammation during respiratory viral infection.

Abstract

Innate immune cells including macrophages, dendritic cells, and granulocytes are resident within or patrol very different microenvironments in the host. Their activity or responsiveness to antigen is dictated by site-specific factors. Because of the constant exposure to environmental antigens and commensal microorganisms, mucosal immunity needs to be more constrained than peripheral counterparts to prevent unnecessary inflammation. The epithelial surfaces that dominate all mucosal tissues provide an ideal regulator since innate immune cells are often in intimate contact with, or lie immediately beneath, them and a breach in epithelial integrity would signal a damaging event and release innate immunity from their influence. We discuss the role of the respiratory epithelium in raising the threshold of innate immune cell activation at homoeostasis, how its absence triggers innate immunity, and how inflammatory resolution often produces an altered homoeostatic environment that can affect the next inflammatory event at this site.