| First Author | Basic M | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 719 |
| PubMed ID | 29335601 | Mgi Jnum | J:259675 |
| Mgi Id | MGI:6148462 | Doi | 10.1038/s41598-017-19062-7 |
| Citation | Basic M, et al. (2018) Loss of CD14 leads to disturbed epithelial-B cell crosstalk and impairment of the intestinal barrier after E. coli Nissle monoassociation. Sci Rep 8(1):719 |
| abstractText | The TLR4 co-receptor CD14 was identified as an IBD candidate gene. Here, its influence on the intestinal barrier was addressed utilizing E. coli Nissle (EcN), which induces severe inflammation in germfree TLR4(-/-) mice. After monoassociation, EcN was detected in spleens and livers of TLR4(-/-) and CD14(-/-) but not wildtype mice. Barrier impairment was characterized by increased apoptosis and decreased epithelial junction (EJ) expression and was reversed by TLR2 stimulation in CD14(-/-) mice. Bone marrow (BM) transplantation revealed contribution of hematopoietic and non-hematopoietic cells towards intestinal homeostasis. EcN inoculated WT mice showed B cell activation, CD14(-/-) and TLR4(-/-) mice cytotoxic T cell and impaired B cell responses. The latter was characterized by absence of B cells in TLR4(-/-) mice, decreased levels of EcN induced immunoglobulins and downregulation of their transporter pIgR. EcN colonization of mice with genetically or antibody induced impaired B cell response resulted in dissemination of EcN and downregulation of EJ. BM chimeras indicated that CD14 originating from radiation resistant cells is sufficient to restore EJ-function. Overall, CD14/TLR4 signalling seems to be critical for intestinal barrier function and for the crosstalk between B cells and the epithelium, underlining that CD14 serves as a protective modulator of intestinal homeostasis. |
