title: Lung cell-specific modulation of LPS-induced TLR4 receptor and adaptor localization.
abstract: Lung infection by Gram-negative bacteria is a major cause of morbidity and mortality in humans. Lipopolysaccharide (LPS), located in the outer membrane of the Gram-negative bacterial cell wall, is a highly potent stimulus of immune and structural cells via the TLR4/MD2 complex whose function is sequentially regulated by defined subsets of adaptor proteins. Regulatory mechanisms of lung-specific defense pathways point at the crucial role of resident alveolar macrophages, alveolar epithelial cells, the TLR4 receptor pathway, and lung surfactant in shaping the innate immune response to Gram-negative bacteria and LPS. During the past decade intracellular spatiotemporal localization of TLR4 emerged as a key feature of TLR4 function. Here, we briefly review lung cell type- and compartment-specific mechanisms of LPS-induced TLR4 regulation with a focus on primary resident hematopoietic and structural cells as well as modifying microenvironmental factors involved.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology; Karolinska Institutet; Stockholm, Sweden.
authors.forename: Vicky
authors.initials: V
authors.lastname: Sender
authors.affiliation: Division of Cellular Pneumology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences; Borstel, Germany ; Department of Anesthesiology, University Hospital of Lübeck, Lübeck, Germany.
authors.forename: Cordula
authors.initials: C
authors.lastname: Stamme
keywords: Gram-negative pneumonia; LPS; Surfactant; Surfactant proteins; TLR receptor localization/trafficking; Toll-like receptor 4; alveolar epithelial cells; alveolar macrophages; lung innate immunity