Abstract
Epithelial barrier function and innate immunity are fundamental to the pathogenesis of inflammatory and infectious disease. Along with plasma membranes, epithelial cells are the primary cellular determinant of epithelial barrier function. The mechanism by which polarized epithelia form a permeability barrier is of fundamental importance to the prevention of many infectious and inflammatory diseases. Moreover, epithelial cells express Toll-like receptors (TLRs) which upon recognition of conserved microbial factors such as lipopolysaccharide (LPS) induce epithelial responses including epithelial cell proliferation, secretion of secretory IgA into the lumen and production mucins and antimicrobial peptides, thereby promoting intestinal barrier function. Understanding gut barrier integrity and regulation of permeability is crucial to increase our understanding of the pathogenesis of intestinal disease. A variety of tests have been developed to assess this barrier, including assessing intestinal epithelial cell proliferation or death, intestinal tight junction status and the consequence of intestinal barrier integrity loss such as increased intestinal permeability and susceptibility to bacterial infection. Using a mouse model, this chapter describes some of the methods to assess the functional integrity of this epithelial barrier and the part played by a TLR signalling pathway.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Turner JR (2009) Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 9:799–809
Harhaj NS, Antonetti DA (2004) Regulation of tight junctions and loss of barrier function in pathophysiology. Int J Biochem Cell Biol 36:1206–1237
Fasano A, Shea-Donohue T (2005) Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol 2:416–422
Balkovetz DF, Katz J (2003) Bacterial invasion by a paracellular route: divide and conquer. Microbes Infect 5:613–619
Corr SC, Palsson-McDermott EM, Grishina I et al (2014) MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C. Mucosal Immunol 7(1):57–67
Gonzalez-Mariscal L, Tapia R, Chamorro D (2008) Crosstalk of tight junction components with signaling pathways. Biochim Biophys Acta 1778:729–756
Guo S, Al-Sadi R, Said HM et al (2013) Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14. Am J Pathol 182(2):375–387
Alenghat T, Osborne LC, Saenz SA et al (2013) Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis. Nature 504:153–157
Cario E, Gerken G, Podolsky DK (2004) Toll-like receptor 2 enhances ZO-1 associated intestinal epithelial barrier integrity via protein kinase C. Gastroenterology 127(1):224–238
Aviello G, Corr SC, Johnston DGW et al (2014) MyD88 adaptor-like (Mal) regulates intestinal homeostasis and colitis-associated colorectal cancer in mice. Am J Physiol 306(9):G769–G778
Brandl K, Sun L, Neppl C (2010) MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands. Proc Natl Acad Sci 107(46):19967–19972
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media New York
About this protocol
Cite this protocol
Johnston, D.G.W., Corr, S.C. (2016). Toll-Like Receptor Signalling and the Control of Intestinal Barrier Function. In: McCoy, C. (eds) Toll-Like Receptors. Methods in Molecular Biology, vol 1390. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3335-8_18
Download citation
DOI: https://doi.org/10.1007/978-1-4939-3335-8_18
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-3333-4
Online ISBN: 978-1-4939-3335-8
eBook Packages: Springer Protocols