Tags

Type your tag names separated by a space and hit enter

Epithelial Myeloid-Differentiation Factor 88 Is Dispensable during Klebsiella Pneumonia.
Am J Respir Cell Mol Biol 2017; 56(5):648-656AJ

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+Show Affiliations

1 Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 2 Center of Experimental and Molecular Medicine.1 Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 2 Center of Experimental and Molecular Medicine.1 Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 3 Department of Anatomy, Embryology, and Physiology, and.1 Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 3 Department of Anatomy, Embryology, and Physiology, and.4 Division of Immunology, Biomedical Sciences Research Center Alexander Flemming, Athens, Greece.1 Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 5 Department of Pathology.1 Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 2 Center of Experimental and Molecular Medicine.6 Institute of Biophysics, Chaoyang District, Beijing, China; and.1 Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 2 Center of Experimental and Molecular Medicine.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28187270

Citation

Anas, Adam A., et al. "Epithelial Myeloid-Differentiation Factor 88 Is Dispensable During Klebsiella Pneumonia." American Journal of Respiratory Cell and Molecular Biology, vol. 56, no. 5, 2017, pp. 648-656.
Anas AA, Claushuis TAM, Mohan RA, et al. Epithelial Myeloid-Differentiation Factor 88 Is Dispensable during Klebsiella Pneumonia. Am J Respir Cell Mol Biol. 2017;56(5):648-656.
Anas, A. A., Claushuis, T. A. M., Mohan, R. A., Christoffels, V. M., Aidinis, V., Florquin, S., ... van der Poll, T. (2017). Epithelial Myeloid-Differentiation Factor 88 Is Dispensable during Klebsiella Pneumonia. American Journal of Respiratory Cell and Molecular Biology, 56(5), pp. 648-656. doi:10.1165/rcmb.2016-0190OC.
Anas AA, et al. Epithelial Myeloid-Differentiation Factor 88 Is Dispensable During Klebsiella Pneumonia. Am J Respir Cell Mol Biol. 2017;56(5):648-656. PubMed PMID: 28187270.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epithelial Myeloid-Differentiation Factor 88 Is Dispensable during Klebsiella Pneumonia. AU - Anas,Adam A, AU - Claushuis,Theodora A M, AU - Mohan,Rajiv A, AU - Christoffels,Vincent M, AU - Aidinis,Vassilis, AU - Florquin,Sandrine, AU - Van't Veer,Cornelis, AU - Hou,Baidong, AU - de Vos,Alex F, AU - van der Poll,Tom, PY - 2017/2/12/pubmed PY - 2017/8/2/medline PY - 2017/2/11/entrez KW - Klebsiella KW - Toll-like receptor KW - lung epithelial KW - myeloid-differentiation factor 88 KW - pneumonia SP - 648 EP - 656 JF - American journal of respiratory cell and molecular biology JO - Am. J. Respir. Cell Mol. Biol. VL - 56 IS - 5 N2 - 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. SN - 1535-4989 UR - https://www.unboundmedicine.com/medline/citation/28187270/Epithelial_Myeloid_Differentiation_Factor_88_Is_Dispensable_during_Klebsiella_Pneumonia_ L2 - http://www.atsjournals.org/doi/full/10.1165/rcmb.2016-0190OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -