Loss of CD14 leads to disturbed epithelial-B cell crosstalk and impairment of the intestinal barrier after E. coli Nissle monoassociation
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 CD...
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Published in | Scientific reports Vol. 8; no. 1; pp. 719 - 14 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
15.01.2018
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-017-19062-7 |