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 c... More
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.
