Role(s) of Pulmonary Macrophage and Dendritic Cells in SARS-CoV-Induced Host Inflammatory Responses: An in vitro Model. (43.39)

Abstract

Abstract SARS is a highly contagious respiratory disease with the lungs as a major target. Pulmonary macrophage (MΦ), airway epithelium, and dendritic cells (DC) are three key cells in host innate defenses against respiratory infections. Pulmonary MΦ are situated at the inner epithelial surface, whereas DC reside abundantly underneath the epithelium. Such strategic anatomic locations of these two effector cells within the airway system make it highly relevant and important to investigate their interrelationship with airway epithelial cells in the course of SARS coronavirus (SARS-CoV) infection. In this study, we established highly polarized human bronchial Calu-3 cell cultures in transwell membrane inserts which allowed us to harvest cytokines produced by the apical or the basolateral surfaces of SARS-CoV-infected Calu-3 cells. Here, we report that inflammatory cytokines released by infected Calu-3 cells differ between the two surfaces and are potent in modulating the intrinsic functions of both MΦ and DC. Specifically, they prompt the production of various inflammatory mediators by both MΦ and DC. However, they also significantly compromised the abilities of DC and MΦ in priming naive T cells and phagocytosis, respectively. These results suggest that the interplays among permissive lung epithelial cells, pulmonary MΦ and DC are critically involved in the regulation of inflammatory responses in the course of acute SARS-CoV infection and pathogenesis.