Targeted deletion of MyD88 in intestinal epithelial cells results in compromised antibacterial immunity associated with downregulation of polymeric immunoglobulin receptor, mucin-2, and antibacterial peptides
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Intestinal epithelial cells (IECs) form a physical and immunological barrier that separates the vast gut microbiota from host tissues. MyD88-dependent Toll-like receptor signaling is a key mediator of microbial-host cross-talk. We examined the role of epithelial MyD88 expression by generating mice with an IEC-targeted deletion of the Myd88 gene (MyD88(ΔIEC)). Loss of epithelial MyD88 signaling resulted in increased numbers of mucus-associated bacteria; translocation of bacteria, including the opportunistic pathogen Klebsiella pneumoniae, to mesenteric lymph nodes; reduced transmucosal electrical resistance; impaired mucus-associated antimicrobial activity; and downregulated expression of polymeric immunoglobulin receptor (the epithelial IgA transporter), mucin-2 (the major protein of intestinal mucus), and the antimicrobial peptides RegIIIγ and Defa-rs1. We further observed significant differences in the composition of the gut microbiota between MyD88(ΔIEC) mice and wild-type littermates. These physical, immunological, and microbial defects resulted in increased susceptibility of MyD88(ΔIEC) mice to experimental colitis. We conclude that MyD88 signaling in IECs is crucial for maintenance of gut homeostasis.
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Both TM7 and Proteobacteria are found at increased levels in the altered flora after epithelial cell-specific ablation of MyD88.
“Both TM7 and Proteobacteria are found at increased levels in the altered flora after epithelial cell-specific ablation of MyD88 50.”
From The composition of the gut microbiota shapes the colon mucus barrier (2015) · cites this paper as [50]
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Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554 · see citing works
Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis
Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S., & Medzhitov, R. (2004) · Cell · doi:10.1016/j.cell.2004.07.002 · Cited by 4,251 · see citing works
Intestinal mucosal barrier function in health and disease
Turner, J. R. (2009) · Nature reviews. Immunology · doi:10.1038/nri2653 · Cited by 3,952 · see citing works
Interactive Tree Of Life (iTOL): an online tool for phylogenetic tree display and annotation
Letunić, I., & Peer Bork, B. (2006) · Bioinformatics · doi:10.1093/bioinformatics/btl529 · Cited by 3,326 · see citing works
UniFrac: an effective distance metric for microbial community comparison
Lozupone, C., Lladser, M. E., Knights, D., Stombaugh, J., & Knight, R. (2011) · The ISME Journal · doi:10.1038/ismej.2010.133 · Cited by 2,825 · see citing works
Genetics and pathogenesis of inflammatory bowel disease
Khor, B., Gardet, A., & Xavier, R. J. (2011) · Nature · doi:10.1038/nature10209 · Cited by 2,629 · see citing works
Direct multiplexed measurement of gene expression with color-coded probe pairs
Geiss, G. K., Bumgarner, R. E., Birditt, B., Dahl, T., Dowidar, N., Dunaway, D. L., Fell, H. P., Ferree, S., George, R. D., Grogan, T., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1385 · Cited by 2,066 · see citing works
NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis
Elinav, E., Strowig, T., Kau, A. L., Henao-Mejia, J., Thaiss, C. A., Booth, C. J., Peaper, D. R., Bertin, J., Eisenbarth, S. C., Gordon, J. I., et al. (2011) · Cell · doi:10.1016/j.cell.2011.04.022 · Cited by 2,024 · see citing works
Intestinal homeostasis and its breakdown in inflammatory bowel disease
Maloy, K. J., & Powrie, F. M. (2011) · Nature · doi:10.1038/nature10208 · Cited by 1,876 · see citing works
Immune adaptations that maintain homeostasis with the intestinal microbiota
Hooper, L. V., & Macpherson, A. J. (2010) · Nature reviews. Immunology · doi:10.1038/nri2710 · Cited by 1,455 · see citing works
Symbiotic bacteria direct expression of an intestinal bactericidal lectin
Cash, H. L., Whitham, C. V., Behrendt, C. L., & Hooper, L. V. (2006) · Science · doi:10.1126/science.1127119 · Cited by 1,432 · see citing works
Vaishnava, S., Yamamoto, M., Severson, K. M., Ruhn, K. A., Yu, X., Koren, O., Ley, R., Wakeland, E. K., & Hooper, L. V. (2011) · Science · doi:10.1126/science.1209791 · Cited by 1,412 · see citing works
Abreu, M. T. (2010) · Nature Reviews Immunology · doi:10.1038/nri2707 · Cited by 1,288 · see citing works
Pyogenic Bacterial Infections in Humans with MyD88 Deficiency
von Bernuth, H., Pïcard, C., Jin, Z., Sranujit, R. P., Xiao, H. Q., Ku, C., Chrabieh, M., Ben‐Mustapha, I., Ghandil, P., Çamcıoğlu, Y., et al. (2008) · Science · doi:10.1126/science.1158298 · Cited by 1,287 · see citing works
Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut
Mantis, N. J., Rol, N., & Corthésy, B. (2011) · Mucosal Immunology · doi:10.1038/mi.2011.41 · Cited by 1,283 · see citing works
Mucins in the mucosal barrier to infection
Lindén, S. K., SUTTON, P. R. N., Karlsson, N. G., Korolik, V., & McGuckin, M. A. (2008) · Mucosal Immunology · doi:10.1038/mi.2008.5 · Cited by 1,241 · see citing works
The immune geography of IgA induction and function
Macpherson, A. J., McCoy, K. D., Johansen, F.-E., & Brandtzaeg, P. (2007) · Mucosal Immunology · doi:10.1038/mi.2007.6 · Cited by 1,047 · see citing works
Garrett, W. S., Gallini, C. A., Yatsunenko, T., Michaud, M., DuBois, A., Delaney, M. L., Punit, S., Karlsson, M., Bry, L., Glickman, J. N., et al. (2010) · Cell Host & Microbe · doi:10.1016/j.chom.2010.08.004 · Cited by 788 · see citing works
Regularized linear discriminant analysis and its application in microarrays
Guo, Y., Hastie, T. J., & Tibshirani, R. (2006) · Biostatistics · doi:10.1093/biostatistics/kxj035 · Cited by 598 · see citing works
Colombo, A. P. V., Boches, S. K., Cotton, S. L., Goodson, J. M., Kent, R., Haffajee, A. D., Socransky, S. S., Hastürk, H., Dyke, T. E. V., Dewhirst, F. E., et al. (2009) · Journal of Periodontology · doi:10.1902/jop.2009.090185 · Cited by 562 · see citing works
Fukata, M., Michelsen, K. S., Eri, R. D., Thomas, L. S., Hu, B., Lukasek, K., Nast, C. C., Lechago, J., Xu, R., Naiki, Y., et al. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00328.2004 · Cited by 508 · see citing works
Isolation and subsequent analysis of murine lamina propria mononuclear cells from colonic tissue
Weigmann, B., Tubbe, I., Seidel, D., Nicolaev, A., Becker, C., & Neurath, M. F. (2007) · Nature Protocols · doi:10.1038/nprot.2007.315 · Cited by 483 · see citing works
The Commensal Microbiota and Enteropathogens in the Pathogenesis of Inflammatory Bowel Diseases
Chassaing, B., & Darfeuille–Michaud, A. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.01.054 · Cited by 443 · see citing works
Casanova, J., Abel, L., & Quintana‐Murci, L. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101335 · Cited by 369 · see citing works
Johansen, F.-E., & Kaetzel, C. S. (2011) · Mucosal Immunology · doi:10.1038/mi.2011.37 · Cited by 368 · see citing works
Self-citationToll-like receptors in inflammatory bowel diseases: A decade later
Cario, E. (2010) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21282 · Cited by 339 · see citing works
Packey, C. D., & Sartor, R. B. (2009) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0b013e32832a8a5d · Cited by 319 · see citing works
Clinical use of E. coli Nissle 1917 in inflammatory bowel disease
Schultz, M. (2008) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20377 · Cited by 310 · see citing works
Ismail, A. S., Severson, K. M., Vaishnava, S., Behrendt, C. L., Yu, X., Benjamin, J. L., Ruhn, K. A., Hou, B., DeFranco, A. L., Yarovinsky, F., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019574108 · Cited by 302 · see citing works
Weber, C. R., Raleigh, D. R., Su, L., Shen, L., Sullivan, E. A., Wang, Y., & Turner, J. R. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.064808 · Cited by 296 · see citing works
Self-citationIntestinal TM7 bacterial phylogenies in active inflammatory bowel disease
Kuehbacher, T., Rehman, A., Lepage, P., Hellmig, S., Fölsch, U. R., Schreiber, S., & Ott, S. J. (2008) · Journal of Medical Microbiology · doi:10.1099/jmm.0.47719-0 · Cited by 190 · see citing works
Secretory IgA: Arresting Microbial Pathogens at Epithelial Borders
Mantis, N. J., & Forbes, S. J. (2010) · Immunological Investigations · doi:10.3109/08820131003622635 · Cited by 185 · see citing works
Moehle, C., Ackermann, N., Langmann, T., Aslanidis, C., Kel, A. E., Kel-Margoulis, O. V., Schmitz-Mądry, A., Zahn, A., Stremmel, W., & Schmitz, G. (2006) · Journal of Molecular Medicine · doi:10.1007/s00109-006-0100-2 · Cited by 180 · see citing works
Toll-Like Receptor–Gut Microbiota Interactions: Perturb at Your Own Risk!
Carvalho, F. A., Aitken, J. D., Vijay–Kumar, M., & Gewirtz, A. T. (2011) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020911-153330 · Cited by 164 · see citing works
Brandl, K., Sun, L., Neppl, C., Siggs, O. M., Gall, S. M. L., Tomisato, W., Li, X., Du, X., Männel, D. N., Blobel, C., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1014669107 · Cited by 145 · see citing works
Pinto, D., Robine, S., Jaisser, F., Marjou, F. E., & Louvard, D. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.10.6476 · Cited by 134 · see citing works
Keeping Bacteria at a Distance
Johansson, M., & Hansson, G. C. (2011) · Science · doi:10.1126/science.1213909 · Cited by 112 · see citing works
Asquith, M. J., Boulard, O., Powrie, F. M., & Maloy, K. J. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.04.045 · Cited by 107 · see citing works
Cai, S., Batra, S., Shen, L., Wakamatsu, N., & Jeyaseelan, S. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901033 · Cited by 102 · see citing works
Self-citationCriss, A. K., Ahlgren, D. M., Jou, T., McCormick, B. A., & Casanova, J. E. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.7.1331 · Cited by 95 · see citing works
Genes and Environment: How Will Our Concepts on the Pathophysiology of IBD Develop in the Future?
Kaser, A., Zeißig, S., & Blumberg, R. S. (2010) · Digestive Diseases · doi:10.1159/000320393 · Cited by 92 · see citing works
Roadblocks in the gut: barriers to enteric infection
Gill, N., Wlodarska, M., & Finlay, B. B. (2011) · Cellular Microbiology · doi:10.1111/j.1462-5822.2011.01578.x · Cited by 87 · see citing works
Bruno, M., Frantz, A. L., Rogier, E. W., Johansen, F.-E., & Kaetzel, C. S. (2011) · Mucosal Immunology · doi:10.1038/mi.2011.8 · Cited by 86 · see citing works
Self-citationSignature biomarkers in Crohn's disease: toward a molecular classification
Arsenescu, R. I., Bruno, M., Rogier, E. W., Stefka, A. T., McMahan, A., Wright, T. B., Nasser, M. S., de Villiers, W. J. S., & Kaetzel, C. S. (2008) · Mucosal Immunology · doi:10.1038/mi.2008.32 · Cited by 78 · see citing works
Self-citationBlanch, V. J., Piskurich, J. F., & Kaetzel, C. S. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.3.1232 · Cited by 74 · see citing works
Self-citationGong, J., Xu, J., Zhu, W., Gao, X., Li, N., & Li, J. (2010) · Clinical Immunology · doi:10.1016/j.clim.2010.04.001 · Cited by 67 · see citing works
Suppression of experimental colitis in mice by CD11c+ dendritic cells
Qualls, J. E., Tuna, H., Kaplan, A. M., & Cohen, D. A. (2008) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20733 · Cited by 61 · see citing works
Self-citationMurthy, A. K., Dubose, C. N., Banas, J. A., Coalson, J. J., & Arulanandam, B. P. (2006) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2006.04312.x · Cited by 59 · see citing works
Bruno, M. E. C., Rogier, E. W., Frantz, A. L., Stefka, A. T., Thompson, S. N., & Kaetzel, C. S. (2010) · Immunological Investigations · doi:10.3109/08820131003622809 · Cited by 57 · see citing works
Self-citationHost and microbiota factors that control Klebsiella pneumoniae mucosal colonization in mice
Lau, H. Y., Huffnagle, G. B., & Moore, T. A. (2008) · Microbes and Infection · doi:10.1016/j.micinf.2008.07.040 · Cited by 49 · see citing works
Macpherson, A. J., Geuking, M. B., & McCoy, K. D. (2011) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e32834bb805 · Cited by 38 · see citing works
Cario, E. (2010) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e32833d4b88 · Cited by 35 · see citing works
Joint Extraintestinal Manifestations in Ulcerative Colitis
Dorofeyev, A. E., Василенко, И. В., & Rassokhina, O. A. (2009) · Digestive Diseases · doi:10.1159/000233289 · Cited by 30 · see citing works
Frantz, A. L., Bruno, M. E. C., Rogier, E. W., Tuna, H., Cohen, D. A., Bondada, S., Chelvarajan, L., Brandon, J. A., Jennings, D. C., & Kaetzel, C. S. (2012) · Inflammatory Bowel Diseases · doi:10.1002/ibd.22923 · Cited by 21 · see citing works
Self-citationLoy, A., Pester, M., & Steger, D. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-947-5_13 · Cited by 10 · see citing works
Is there a role for defensins in IBD?
Wehkamp, J., & Stange, E. F. (2008) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20698 · Cited by 9 · see citing works
MyD88 Signaling in the Intestine: Dr Jekyll and Mr Hyde?
Jobin, C. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.06.027 · Cited by 8 · see citing works
Is there a role for defensins in IBD?
Wehkamp, J., & Stange, E. F. (2008) · Inflammatory Bowel Diseases · doi:10.1097/00054725-200810001-00044 · Cited by 2 · see citing works
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Levy, M., Kolodziejczyk, A. A., Thaiss, C. A., & Elinav, E. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.7 · Cited by 1,769 · see citing works
Control of pathogens and pathobionts by the gut microbiota
Kamada, N., Chen, G. Y., Inohara, N., & Núñez, G. (2013) · Nature Immunology · doi:10.1038/ni.2608 · Cited by 1,625 · see citing works
Immunological aspects of intestinal mucus and mucins
Johansson, M. E. V., & Hansson, G. C. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.88 · Cited by 1,007 · see citing works
Interaction Between the Microbiota, Epithelia, and Immune Cells in the Intestine
Kayama, H., Okumura, R., & Takeda, K. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-070119-115104 · Cited by 765 · see citing works
The human gut microbiota: Metabolism and perspective in obesity
Gomes, A. C., Hoffmann, C., & Mota, J. F. (2018) · Gut Microbes · doi:10.1080/19490976.2018.1465157 · Cited by 745 · see citing works
Interactions of commensal and pathogenic microorganisms with the intestinal mucosal barrier
Martens, E. C., Neumann, M., & Desai, M. S. (2018) · Nature Reviews Microbiology · doi:10.1038/s41579-018-0036-x · Cited by 711 · see citing works
Roles of intestinal epithelial cells in the maintenance of gut homeostasis
Okumura, R., & Takeda, K. (2017) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.20 · Cited by 712 · see citing works
The composition of the gut microbiota shapes the colon mucus barrier
Jakobsson, H. E., Rodríguez‐Piñeiro, A. M., Schütte, A., Ermund, A., Boysen, P., Bemark, M., Sommer, F., Bäckhed, F., Hansson, G. C., & Johansson, M. E. (2015) · The EMBO Reports · doi:10.15252/embr.201439263 · Cited by 700 · see citing works
“Both TM7 and Proteobacteria are found at increased levels in the altered flora after epithelial cell-specific ablation of MyD88 [50].”
The influence of the microbiome on respiratory health
Wypych, T. P., Wickramasinghe, L. C., & Marsland, B. J. (2019) · Nature Immunology · doi:10.1038/s41590-019-0451-9 · Cited by 611 · see citing works
A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion
Birchenough, G. M. H., Nyström, E. E. L., Johansson, M. E. V., & Hansson, G. C. (2016) · Science · doi:10.1126/science.aaf7419 · Cited by 568 · see citing works
Wiertsema, S. P., van Bergenhenegouwen, J., Garssen, J., & Knippels, L. M. J. (2021) · Nutrients · doi:10.3390/nu13030886 · Cited by 558 · see citing works
Rogier, E. W., Frantz, A. L., Bruno, M. E. C., Wedlund, L., Cohen, D. A., Stromberg, A. J., & Kaetzel, C. S. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315792111 · Cited by 484 · see citing works
Self-citationEpithelial Toll-like receptors and their role in gut homeostasis and disease
Burgueño, J. F., & Abreu, M. T. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0261-4 · Cited by 399 · see citing works
Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches
Belizário, J. E., & Napolitano, M. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.01050 · Cited by 377 · see citing works
Maintenance of intestinal homeostasis by mucosal barriers
Okumura, R., & Takeda, K. (2018) · Inflammation and Regeneration · doi:10.1186/s41232-018-0063-z · Cited by 368 · see citing works
The first thousand days - intestinal microbiology of early life: Establishing a symbiosis
Wopereis, H., Oozeer, R., Knipping, K., Belzer, C., & Knol, J. (2014) · Pediatric Allergy and Immunology · doi:10.1111/pai.12232 · Cited by 352 · see citing works
Antimicrobial peptides and gut microbiota in homeostasis and pathology
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Microbiota, Inflammation and Colorectal Cancer
Lucas, C., Barnich, N., & Nguyen, H. T. T. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18061310 · Cited by 318 · see citing works
Host Genetics and Gut Microbiome: Challenges and Perspectives
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Mechanism of the Gut Microbiota Colonization Resistance and Enteric Pathogen Infection
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The impacts of natural polysaccharides on intestinal microbiota and immune responses – a review
Tang, C., Ding, R., Sun, J. G., Liu, J., Kan, J., & Jin, C. (2019) · Food & Function · doi:10.1039/c8fo01946k · Cited by 281 · see citing works
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Francescone, R., Hou, V., & Grivennikov, S. I. (2015) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000236 · Cited by 273 · see citing works
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Everard, A., Geurts, L., Caesar, R., Hul, M. V., Matamoros, S., Duparc, T., Denis, R., Cochez, P. M., Pierard, F., Castel, J., et al. (2014) · Nature Communications · doi:10.1038/ncomms6648 · Cited by 237 · see citing works
Rajca, S., Grondin, V., Louis, E. J., Vernier-Massouille, G., Grimaud, J., Bouhnik, Y., Laharie, D., Dupas, J., Pillant, H., Picon, L., et al. (2014) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000036 · Cited by 236 · see citing works
Moon, C., VanDussen, K. L., Miyoshi, H., & Stappenbeck, T. S. (2013) · Mucosal Immunology · doi:10.1038/mi.2013.98 · Cited by 232 · see citing works
Innate immune signalling at the intestinal epithelium in homeostasis and disease
Pott, J., & Hornef, M. W. (2012) · EMBO Reports · doi:10.1038/embor.2012.96 · Cited by 227 · see citing works
Spiljar, M., Merkler, D., & Trajkovski, M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01353 · Cited by 219 · see citing works
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Antimicrobial peptides and the enteric mucus layer act in concert to protect the intestinal mucosa
Dupont, A., Heinbockel, L., Brandenburg, K., & Hornef, M. W. (2014) · Gut Microbes · doi:10.4161/19490976.2014.972238 · Cited by 141 · see citing works
van der Vaart, M., van Soest, J. J., Spaink, H. P., & Meijer, A. H. (2013) · Disease Models & Mechanisms · doi:10.1242/dmm.010843 · Cited by 134 · see citing works
Chen, J., Li, Y., Tian, Y., Huang, C., Li, D., Zhong, Q., & Ma, X. (2015) · Current Protein and Peptide Science · doi:10.2174/1389203716666150630135720 · Cited by 133 · see citing works
Fusobacterium and Enterobacteriaceae: Important players for CRC?
Allen‐Vercoe, E., & Jobin, C. (2014) · Immunology Letters · doi:10.1016/j.imlet.2014.05.014 · Cited by 132 · see citing works
Mucosal innate immune cells regulate both gut homeostasis and intestinal inflammation
Kurashima, Y., Goto, Y., & Kiyono, H. (2013) · European Journal of Immunology · doi:10.1002/eji.201343782 · Cited by 128 · see citing works
Mucosal immunity in liver autoimmunity: A comprehensive review
Trivedi, P. J., & Adams, D. (2013) · Journal of Autoimmunity · doi:10.1016/j.jaut.2013.06.013 · Cited by 128 · see citing works
Vlantis, K., Polykratis, A., Welz, P.-S., Loo, G., Pasparakis, M., & Wullaert, A. (2015) · Gut · doi:10.1136/gutjnl-2014-308323 · Cited by 126 · see citing works
Gut microbiome and anticancer immune response: really hot Sh*t!
Viaud, S., Daillère, R., Boneca, I. G., Lepage, P., Langella, P., Chamaillard, M., Pittet, M. J., Ghiringhelli, F., Trinchieri, G., Goldszmid, R., et al. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.56 · Cited by 123 · see citing works
Intestinal stromal cells in mucosal immunity and homeostasis
Owens, B. M. J., & Simmons, A. (2012) · Mucosal Immunology · doi:10.1038/mi.2012.125 · Cited by 117 · see citing works
Peng, M., & Biswas, D. (2016) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2016.1203286 · Cited by 119 · see citing works
Neonatal Immune Adaptation of the Gut and Its Role during Infections
Tourneur, E., & Chassin, C. (2013) · Clinical and Developmental Immunology · doi:10.1155/2013/270301 · Cited by 110 · see citing works
Analysis of gene–environment interactions in postnatal development of the mammalian intestine
Rakoff-Nahoum, S., Kong, Y., Kleinstein, S. H., Subramanian, S., Ahern, P. P., Gordon, J. I., & Medzhitov, R. M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1424886112 · Cited by 110 · see citing works
Loss of NHE3 alters gut microbiota composition and influencesBacteroides thetaiotaomicrongrowth
Engevik, M. A., Aihara, E., Montrose, M. H., Shull, G. E., Hassett, D. J., & Worrell, R. T. (2013) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00184.2013 · Cited by 105 · see citing works
Rogier, E. W., Frantz, A. L., Bruno, M. E. C., Wedlund, L., Cohen, D. A., Stromberg, A. J., & Kaetzel, C. S. (2014) · Gut Microbes · doi:10.4161/19490976.2014.969984 · Cited by 103 · see citing works
Self-citationNatividad, J. M., Hayes, C. L., Motta, J., Jury, J., Galipeau, H. J., Philip, V., García‐Ródenas, C. L., Kiyama, H., Berčík, P., & Verdu, E. F. (2013) · Applied and Environmental Microbiology · doi:10.1128/aem.02470-13 · Cited by 101 · see citing works
Zhang, M., Li, M.-F., & Sun, L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106543 · Cited by 100 · see citing works
Okumura, R., & Takeda, K. (2024) · Seminars in Immunopathology · doi:10.1007/s00281-024-01026-5 · Cited by 100 · see citing works
MicroRNAs and the regulation of intestinal homeostasis
Runtsch, M. C., Round, J. L., & Oâ€TMConnell, R. M. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00347 · Cited by 94 · see citing works
Fungi as Part of the Microbiota and Interactions with Intestinal Bacteria
Kapitan, M., Niemiec, M. J., Steimle, A., Frick, J.-S., & Jacobsen, I. D. (2018) · Current topics in microbiology and immunology · doi:10.1007/82_2018_117 · Cited by 93 · see citing works
Zhao, Y. N., Yan, Y., Zhou, W., Chen, D., Huang, K., Yu, S., Mi, J., Lu, L., Zeng, X., & Cao, Y. (2020) · Journal of Functional Foods · doi:10.1016/j.jff.2020.104057 · Cited by 92 · see citing works
Lin, X., Gaudino, S. J., Jang, K. K., Bahadur, T., Singh, A. A., Banerjee, A., Beaupre, M., Chu, T. H., Wong, H. T., Kim, C.-K., et al. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.016 · Cited by 92 · see citing works
Microbiome in Multiple Sclerosis: Where Are We, What We Know and Do Not Know
Boziki, M. K., Kesidou, E., Theotokis, P., Mentis, A. A., Karafoulidou, E., Melnikov, M., Sviridova, A. A., Rogovskii, V., Boyко, A., & Grigoriadis, N. (2020) · Brain Sciences · doi:10.3390/brainsci10040234 · Cited by 90 · see citing works
Intestinal barrier homeostasis in inflammatory bowel disease
Goll, R., & Granlund, A. V. B. (2014) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2014.971425 · Cited by 91 · see citing works
Bhinder, G., Stahl, M., Sham, H. P., Crowley, S. M., Morampudi, V., Dalwadi, U., Ma, C., Jacobson, K., & Vallance, B. A. (2014) · Infection and Immunity · doi:10.1128/iai.02045-14 · Cited by 87 · see citing works
Putnam, N. E., Fulbright, L. E., Curry, J. M., Ford, C. A., Petronglo, J. R., Hendrix, A. S., & Cassat, J. E. (2019) · PLoS Pathogens · doi:10.1371/journal.ppat.1007744 · Cited by 86 · see citing works
Sham, H. P., Yu, E. Y. S., Gulen, M. F., Bhinder, G., Stahl, M., Chan, J. M., Brewster, L., Morampudi, V., Gibson, D. L., Hughes, M. R., et al. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003539 · Cited by 83 · see citing works
Chen, X., Sun, W., Xu, B., Wu, E., Cui, Y., Hao, K., Zhang, G., Zhou, C., Xu, Y., Jiang, L., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.766296 · Cited by 76 · see citing works
Riedel, S., Pheiffer, C., Johnson, R., Louw, J., & Muller, C. J. F. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.833544 · Cited by 73 · see citing works
Parenteral Nutrition-Associated Liver Disease: The Role of the Gut Microbiota
Cahová, M., Brátová, M., & Wohl, P. (2017) · Nutrients · doi:10.3390/nu9090987 · Cited by 71 · see citing works
Milligan‐McClellan, K., Small, C. M., Mittge, E., Agarwal, M., Currey, M. C., Cresko, W. A., & Guillemin, K. J. (2015) · Disease Models & Mechanisms · doi:10.1242/dmm.021881 · Cited by 68 · see citing works
The Role of Gut Microbiota and Metabolites in Obesity-Associated Chronic Gastrointestinal Disorders
Islam, M. R., Arthur, S., Haynes, J., Butts, M. R., Nepal, N., & Sundaram, U. (2022) · Nutrients · doi:10.3390/nu14030624 · Cited by 68 · see citing works
New paradigms for functional HIV-specific nonneutralizing antibodies
Forthal, D. N., Hope, T. J., & Alter, G. (2013) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0b013e328363d486 · Cited by 64 · see citing works
The microbiota: a crucial mediator in gut homeostasis and colonization resistance
Chen, Y., Xiao, L., Zhou, M., & Zhang, H. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1417864 · Cited by 69 · see citing works
Dendritic cell–epithelial cell crosstalk in the gut
Rescigno, M. (2014) · Immunological Reviews · doi:10.1111/imr.12181 · Cited by 60 · see citing works
Toll Like Receptors as Sensors of the Tumor Microbial Dysbiosis: Implications in Cancer Progression
Noci, V. L., Bernardo, G., Bianchi, F., Tagliabue, E., Sommariva, M., & Sfondrini, L. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.732192 · Cited by 59 · see citing works
Immune and genetic gardening of the intestinal microbiome
Jacobs, J. P., & Braun, J. G. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.02.052 · Cited by 56 · see citing works
Runtsch, M. C., Hu, R., Alexander, M., Wallace, J. A., Kagele, D., Petersen, C., Valentine, J. F., Welker, N. C., Bronner, M. P., Chen, X., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5597 · Cited by 57 · see citing works
Dey, P., Chaudhuri, S. R., Efferth, T., & Pal, S. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.09.026 · Cited by 57 · see citing works
CRC—all about microbial products and barrier function?
Jobin, C. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.220 · Cited by 51 · see citing works
Mouse and human Notch-1 regulate mucosal immune responses
Mathern, D. R., Laitman, L. E., Hovhannisyan, Z., Dunkin, D., Farsio, S., Malik, T. J., Roda, G., Chitre, A. S., Iuga, A. C., Yeretssian, G., et al. (2014) · Mucosal Immunology · doi:10.1038/mi.2013.118 · Cited by 51 · see citing works
Mizraji, G., Nassar, M., Segev, H., Sharawi, H., Eli‐Berchoer, L., Capucha, T., Nir, T., Tabib, Y., Maimon, A., Dishon, S., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.047 · Cited by 50 · see citing works
The microbiome and childhood diseases: Focus on brain‐gut axis
O’Mahony, S. M., Stilling, R. M., Dinan, T. G., & Cryan, J. F. (2015) · Birth Defects Research Part C Embryo Today Reviews · doi:10.1002/bdrc.21118 · Cited by 50 · see citing works
Advances in intestinal epithelium and gut microbiota interaction
Yang, S., Liu, H., & Liu, Y. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1499202 · Cited by 48 · see citing works
The bidirectional nature of microbiome-epithelial cell interactions
Solis, A. G., Klapholz, M., Zhao, J., & Levy, M. (2020) · Current Opinion in Microbiology · doi:10.1016/j.mib.2020.06.007 · Cited by 47 · see citing works
Gut feelings of safety: tolerance to the microbiota mediated by innate immune receptors
Świątczak, B., & Cohen, I. R. (2015) · Microbiology and Immunology · doi:10.1111/1348-0421.12318 · Cited by 45 · see citing works
Intestinal Stem Cell-on-Chip to Study Human Host-Microbiota Interaction
Siwczak, F., Loffet, E. A., Kaminska, M., Koceva, H., Mahé, M. M., & Mosig, A. S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.798552 · Cited by 44 · see citing works
Enterococci and Their Interactions with the Intestinal Microbiome
Dubin, K. A., & Pamer, E. G. (2018) · ASM Press eBooks · doi:10.1128/9781555819705.ch13 · Cited by 43 · see citing works
Microbiota and epigenetics: promising therapeutic approaches?
El-Sayed, A., Aleya, L., & Kamel, M. S. (2021) · Environmental Science and Pollution Research · doi:10.1007/s11356-021-15623-6 · Cited by 41 · see citing works
Bruno, M. E. C., Rogier, E. W., Arsenescu, R. I., Flomenhoft, D. R., Kurkjian, C. J., Ellis, G. I., & Kaetzel, C. S. (2015) · Digestive Diseases and Sciences · doi:10.1007/s10620-015-3700-2 · Cited by 41 · see citing works
Self-citationMcGuckin, M. A., Thornton, D. J., & Whitsett, J. A. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-415847-4.00014-8 · Cited by 40 · see citing works
Kaetzel, C. S. (2014) · ISRN Immunology · doi:10.1155/2014/541537 · Cited by 40 · see citing works
Self-citationContribution of microbiota to the intestinal physicochemical barrier
Malago, J. J. (2014) · Beneficial Microbes · doi:10.3920/bm2014.0041 · Cited by 39 · see citing works
Sivick, K. E., Arpaia, N., Reiner, G. L., Lee, B. L., Russell, B. R., & Barton, G. M. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.01.013 · Cited by 39 · see citing works
TICAM2-related pathway mediates neutrophil exhaustion
Lin, R., Zhang, Y., Pradhan, K., & Li, L. (2020) · Scientific Reports · doi:10.1038/s41598-020-71379-y · Cited by 37 · see citing works
Microbial signals, MyD88, and lymphotoxin drive TNF-independent intestinal epithelial tissue damage
Rusu, I., Mennillo, E., Li, Z., Bain, J. L., Sun, X., Ly, K., Rosli, Y. Y., Naser, M., Wang, Z., Advincula, R., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci154993 · Cited by 36 · see citing works
The gut mucus network: A dynamic liaison between microbes and the immune system
Inaba, R., Vujakovic, S., & Bergstrom, K. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101807 · Cited by 35 · see citing works
Coleman, O. I., Ahl, D., Pin, C., Holm, L. P., Carding, S. R., & Juge, N. (2014) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00218.2013 · Cited by 35 · see citing works
Friedrich, C., Mamareli, P., Thiemann, S., Kruse, F., Wang, Z., Holzmann, B., Strowig, T., Sparwasser, T. D., & Lochner, M. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006357 · Cited by 35 · see citing works
Corr, S. C., Pålsson‐McDermott, E. M., Grishina, I., Barry, S. P., Aviello, G., Bernard, N. J., Casey, P. G., Ward, J. B. J., Keely, S. J., Dandekar, S., et al. (2013) · Mucosal Immunology · doi:10.1038/mi.2013.24 · Cited by 34 · see citing works
Guo, M., Liu, X., Tan, Y., Kang, F.-Y., Zhu, X.-H., Fan, X., Wang, C., Wang, R., Liu, Y., Qin, X., et al. (2021) · Food & Function · doi:10.1039/d1fo01351c · Cited by 30 · see citing works
- Authors
- Frantz, A. L., Rogier, E. W., Weber, C. R., Shen, L., Cohen, D. A., Fenton, L. A., Bruno, M. E. C., & Kaetzel, C. S.
- Affiliations
- University of Kentucky (US)
- University of Chicago (US)
- Corresponding author
- Kaetzel, C S
- Venue
- Mucosal Immunology
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 5
- Issue
- 5
- Pages
- 501-512
- ISSN
- 1933-0219 (ISSN-L)
- PMC
- PMC3422608
- OpenAlex
- W2015015427
- Cited by
- 230
- References
- 57
- Citations by year
- 2026: 7 · 2025: 18 · 2024: 15 · 2023: 8 · 2022: 11 · 2021: 20 · 2020: 9 · 2019: 10 · 2018: 13 · 2017: 22 · 2016: 9 · 2015: 22 · 2014: 39 · 2013: 20 · 2012: 6
- FWCI
- 12.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Mucosal Immunology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Crohn's and Colitis Foundation
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R21AI069027)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- MyD88, intestinal epithelial cells, Toll-like receptor signaling, antibacterial immunity, polymeric immunoglobulin receptor, MUC2, antimicrobial peptides, RegIIIγ, Klebsiella pneumoniae, bacterial translocation, mucus-associated bacteria, gut microbiota, colitis susceptibility, intestinal barrier, intestinal homeostasis
- MeSH terms
- Pancreatitis-Associated Proteins, Animals, Cell Line, Colitis, Homeostasis, Humans, Intestinal Mucosa, Klebsiella Infections, Klebsiella pneumoniae, Mice, Inbred C57BL, Opportunistic Infections, Peptide Fragments, Proteins, Signal Transduction, Down-Regulation, Sequence Deletion, Mice, Knockout, Immunity, Mucosal, Receptors, Polymeric Immunoglobulin, Models, Animal, RNA, Small Interfering, Mice, Myeloid Differentiation Factor 88, Metagenome, Mucin-2
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