Epithelial Myeloid-Differentiation Factor 88 Is Dispensable during Klebsiella Pneumonia.

Adam A Anas, Theodora A M Claushuis, Rajiv A Mohan, Vincent M Christoffels, Vassilis Aidinis, Sandrine Florquin, Cornelis Van't Veer, Baidong Hou, Alex F de Vos, Tom van der Poll

American journal of respiratory cell and molecular biology 2017 May

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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.

Citation

Adam A Anas, Theodora A M Claushuis, Rajiv A Mohan, Vincent M Christoffels, Vassilis Aidinis, Sandrine Florquin, Cornelis Van't Veer, Baidong Hou, Alex F de Vos, Tom van der Poll. Epithelial Myeloid-Differentiation Factor 88 Is Dispensable during Klebsiella Pneumonia. American journal of respiratory cell and molecular biology. 2017 May;56(5):648-656