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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...

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Detalles Bibliográficos
Autores principales: Basic, Marijana, Buettner, Manuela, Keubler, Lydia M., Smoczek, Anna, Bruesch, Inga, Buchheister, Stephanie, Bleich, André
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768714/
https://www.ncbi.nlm.nih.gov/pubmed/29335601
http://dx.doi.org/10.1038/s41598-017-19062-7
Descripción
Sumario: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.