Involvement of caveolae in the uptake of respiratory syncytial virus antigen by dendritic cells

Abstract

The uptake of respiratory syncytial virus (RSV) antigen by cattle dendritic cells was investigated. Pathways of antigen uptake were monitored by flow cytometry using specific tracers and by proliferation assays, which were used to measure the presentation of RSV antigen and ovalbumin. Inhibitors that differentially affected pathways were used to distinguish them. Presentation of RSV antigen, but not ovalbumin, was inhibited by phorbol myristate acetate and filipin, which have been reported to inhibit caveolae, but not by cytochalasin D, amiloride, or mannose. These inhibitors have been reported to block macropinocytosis and other actin-dependent uptake mechanisms, endocytic pathways involving clathrin-coated pits, and the mannose receptor. Furthermore, co-localization of RSV antigen and caveolae was observed by confocal microscopy. Thus, the major route for uptake of RSV antigen by cattle dendritic cells is one mediated by caveolae, adding a pathway of antigen uptake by dendritic cells to those established. J. Leukoc. Biol. 66: 50-58; 1999.

Altered Arachidonate Distribution in Macrophages from Caveolin-1 Null Mice Leading to Reduced Eicosanoid Synthesis

“…Caveolin-1 and caveolae are also present in all innate immune cells, although their expression level and distribution appear to strikingly depend on the activation and/or maturation state of the cell (16). Caveolin-1 has been unambiguously identified in murine macrophages and mast cells (18,(51)(52)(53) as well as human dendritic cells and neutrophils (54,55).…”

Reduced clearance of respiratory syncytial virus infection in a preterm lamb model

“…Most of the mononuclear cell staining in this current study was morphologically consistent with macrophages, and given the intracytoplasmic viral inclusions, direct RSV infection of macrophages was most likely. Other mononuclear cells such as dendritic cells and lymphocytes cannot be excluded, as in vitro studies have shown capacity for RSV uptake [44,45]. As for neutrophil antigen accumulation, phagocytosis of sloughed infected cellular debris in airways probably allowed for much of the neutrophil staining, since there was a lack of distinct cytoplasmic inclusions, and the quick demise of the degenerate neutrophil following exocytosis into the airway lumen would prevent opportunity for adequate viral replication.…”

Structural and Functional Aspects of the Small Hydrophobic (SH) Protein in the Human Respiratory Syncytial Virus

“…Lipid rafts are enriched in cholesterol and sphingolipids and form a platform for various protein-protein interactions necessary during signal transduction events (Dykstra et al, 2003), protein trafficking (Helms & Zurzolo, 2004), and also virus entry, assembly, and budding (Suzuki & Suzuki, 2006). Indeed, hRSV has been shown to utilize lipid rafts, and in particular caveolae, a caveolin-1 enriched subdomain (Werling et al, 1999;Brown et al, 2002), to gain entry and in the assembly of virus particles. Only a very low amount of SH protein is associated with the viral envelope (Rixon et al, 2004).…”