Loss of CD14 leads to disturbed epithelial-B cell crosstalk and impairment of the intestinal barrier after E. coli Nissle monoassociation

• Published in: Scientific reports Vol. 8; no. 1; pp. 719 - 14
• Main Authors: Basic, Marijana, Buettner, Manuela, Keubler, Lydia M., Smoczek, Anna, Bruesch, Inga, Buchheister, Stephanie, Bleich, André
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.01.2018; Nature Publishing Group
• Subjects: 13; 13/1; 13/31; 38; 38/39; 38/61; 38/77; 38/90; 631/250/347; 64; 64/60; 692/4020/1503/1581/257; 82/1; 82/51; 82/80; Apoptosis; Bone marrow transplantation; CD14 antigen; Cell activation; Chimeras; Colonization; Cytotoxicity; E coli; Epithelium; Germfree; Homeostasis; Humanities and Social Sciences; Immunoglobulins; Intestine; Lymphocytes B; Lymphocytes T; multidisciplinary; Recovery of function; Science; Science (multidisciplinary); T cell receptors; TLR2 protein; TLR4 protein; Toll-like receptors; Transplantation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-19062-7

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.