title: Lung epithelium as a sentinel and effector system in pneumonia--molecular mechanisms of pathogen recognition and signal transduction.
abstract: Pneumonia, a common disease caused by a great diversity of infectious agents is responsible for enormous morbidity and mortality worldwide. The bronchial and lung epithelium comprises a large surface between host and environment and is attacked as a primary target during lung infection. Besides acting as a mechanical barrier, recent evidence suggests that the lung epithelium functions as an important sentinel system against pathogens. Equipped with transmembranous and cytosolic pathogen-sensing pattern recognition receptors the epithelium detects invading pathogens. A complex signalling results in epithelial cell activation, which essentially participates in initiation and orchestration of the subsequent innate and adaptive immune response. In this review we summarize recent progress in research focussing on molecular mechanisms of pathogen detection, host cell signal transduction, and subsequent activation of lung epithelial cells by pathogens and their virulence factors and point to open questions. The analysis of lung epithelial function in the host response in pneumonia may pave the way to the development of innovative highly needed therapeutics in pneumonia in addition to antibiotics.
authors.affiliation: Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany. stefan.hippenstiel@charite.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Hippenstiel
authors.forename: Bastian
authors.initials: B
authors.lastname: Opitz
authors.forename: Bernd
authors.initials: B
authors.lastname: Schmeck
authors.forename: Norbert
authors.initials: N
authors.lastname: Suttorp
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis; D000818:Animals; D003428:Cross Infection / Q000276:immunology* / Q000382:microbiology; D003600:Cytosol / Q000276:immunology / Q000382:microbiology; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D004848:Epithelium / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D050835:Interferon Regulatory Factors / Q000096:biosynthesis; D007370:Interferon Type I / Q000096:biosynthesis / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000382:microbiology* / Q000821:virology; D016328:NF-kappa B / Q000096:biosynthesis; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology; D011024:Pneumonia, Viral / Q000276:immunology* / Q000382:microbiology; D043562:Receptors, G-Protein-Coupled / Q000276:immunology; D051192:Receptors, Pattern Recognition / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000382:microbiology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology; D037521:Virulence Factors / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050835:Interferon Regulatory Factors; D007370:Interferon Type I; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D043562:Receptors, G-Protein-Coupled; D051192:Receptors, Pattern Recognition; D051193:Toll-Like Receptors; D037521:Virulence Factors