Lung surveillance revealed by two-photon live imaging (103.3)

Abstract

Abstract The lung is a major mucosal site of allergen and pathogen encounter and is also the site of damage resulting in immune-based repair. Despite the interest in how immune cells enter and function in this organ, direct observation of these events has not been possible due to obligate movements made during respiration and blood flow. Real-time imaging of cellular and sub-cellular dynamics in the lung requires image resolution, image-registration, and intact physiology to be simultaneously optimized. We have developed both in vitro slice and intravital stabilized imaging systems. We have applied these methods to visualize how phagocytes function along this mucosal surface. Imaging under basal conditions reveals constitutive surveillance of the alveolar surface by resident dendritic cells (DC). These DCs actively sweep the epithelium, taking up model antigens, whereas alveolar macrophages (AMs) lie immotile within the alveolar space. DC number dramatically increases after allergen challenge; however, sampling behavior is not affected, leading to increased antigen uptake by these proinflammatory cells. These antigen-positive DCs then play a critical role in the activation of T cells visualized in this system. We will discuss the integration of innate and adaptive cells as it occurs in the lung.