title: Epithelial Myeloid-Differentiation Factor 88 Is Dispensable during Klebsiella Pneumonia.
abstract: Klebsiella pneumoniae is a common cause of pneumonia. Previous studies have documented an important role for Toll-like receptors (TLRs) expressed by myeloid cells in the recognition of K. pneumoniae and the initiation of a protective immune response. Lung epithelial cells also express TLRs and can participate in innate immune defense. The aim of this study was to examine the role of the common TLR adaptor protein myeloid-differentiation factor (MyD) 88 in lung epithelium during host defense against K. pneumoniae-induced pneumonia. To this end, we first crossed mice expressing cre recombinase under the control of the surfactant protein C (SftpCcre) or the club cell 10 kD (CC10cre) promoter with reporter mice to show that SftpCcre mice mainly express cre in type II alveolar cells, whereas CC10cre mice express cre almost exclusively in bronchiolar epithelial cells. We then generated mice with cell-targeted deletion of MyD88 in type II alveolar (SftpCcre-MyD88-lox) and bronchiolar epithelial (CC10cre-MyD88-lox) cells, and infected them with K. pneumoniae via the airways. Bacterial growth and dissemination were not affected by the loss of MyD88 in SftpCcre-MyD88-lox or CC10cre-MyD88-lox mice compared with control littermates. Furthermore, inflammatory responses induced by K. pneumoniae in the lung were not dependent on MyD88 expression in type II alveolar or bronchiolar epithelial cells. These results indicate that MyD88 expression in two distinct lung epithelial cell types does not contribute to host defense during pneumonia caused by a common human gram-negative pathogen.
authors.affiliation: 1 Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|2 Center of Experimental and Molecular Medicine.
authors.forename: Adam A
authors.initials: AA
authors.lastname: Anas
authors.affiliation: 1 Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|2 Center of Experimental and Molecular Medicine.
authors.forename: Theodora A M
authors.initials: TAM
authors.lastname: Claushuis
authors.affiliation: 1 Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|3 Department of Anatomy, Embryology, and Physiology, and.
authors.forename: Rajiv A
authors.initials: RA
authors.lastname: Mohan
authors.affiliation: 1 Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|3 Department of Anatomy, Embryology, and Physiology, and.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Christoffels
authors.affiliation: 4 Division of Immunology, Biomedical Sciences Research Center Alexander Flemming, Athens, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Aidinis
authors.affiliation: 1 Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|5 Department of Pathology.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.affiliation: 1 Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|2 Center of Experimental and Molecular Medicine.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Van't Veer
authors.affiliation: 6 Institute of Biophysics, Chaoyang District, Beijing, China; and.
authors.forename: Baidong
authors.initials: B
authors.lastname: Hou
authors.affiliation: 1 Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|2 Center of Experimental and Molecular Medicine.
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.affiliation: 1 Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|2 Center of Experimental and Molecular Medicine.|7 Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D055745:Bronchioles / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D019426:Integrases / Q000378:metabolism; D007710:Klebsiella Infections / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D007711:Klebsiella pneumoniae / Q000502:physiology*; D051379:Mice; D050296:Microbial Viability; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D018410:Pneumonia, Bacterial / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D037721:Pulmonary Surfactant-Associated Protein C / Q000378:metabolism; D014598:Uteroglobin / Q000378:metabolism
chemical_list: D053594:Myeloid Differentiation Factor 88; D037721:Pulmonary Surfactant-Associated Protein C; C556390:Scgb1a1 protein, mouse; D014598:Uteroglobin; C045073:Cre recombinase; D019426:Integrases
keywords: Klebsiella; Toll-like receptor; lung epithelial; myeloid-differentiation factor 88; pneumonia