Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells

By K. Atarashi, Takeshi Tanoue, M. Ando, N. Kamada, Yuji Nagano, S. Narushima, Wataru Suda, A. Imaoka, H. Setoyama, Takashi Nagamori and 21 more. Cell, 2015

971 citations recorded by the source corpus.

SUMMARY Intestinal Th17 cells are induced and accumulate in response to colonization with a subgroup of intestinal microbes such as segmented filamentous bacteria (SFB) and certain extracellular pathogens. Here, we show that adhesion of microbes to intestinal epithelial cells (ECs) is a critical cue for Th17 induction. Upon monocolonization of germ-free mice or rats with SFB indigenous to mice (M-SFB) or rats (R-SFB), M-SFB and R-SFB showed host-specific adhesion to small intestinal ECs, accompanied by host-specific induction of Th17 cells. Citrobacter rodentium and Escherichia coli O157 triggered similar Th17 responses, whereas adhesion-defective mutants of these microbes failed to do so. Moreover, a mixture of 20 bacterial strains, which were selected and isolated from fecal samples of a patient with ulcerative colitis on the basis of their ability to cause a robust induction of Th17 cells in the mouse colon, also exhibited EC-adhesive characteristics.

Subfields: Genetics, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/fb425c6e10407001ba923dcb89ec40fe5cb145d0

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In Genetics

1. G. Núñez
2. Eran Segal
3. Lan Lin
4. Steffen Jung
5. Jianqiong Zhang
6. Y. Belkaid
7. S. Gaffen

In Immunology

1. O. Harrison
2. Y. Belkaid
3. S. Gaffen
4. D. Cua
5. Steffen Jung
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In Molecular Biology

1. Y. Belkaid
2. O. Harrison
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4. M. Zeng
5. Y. Taur
6. Eyal David
7. G. Núñez
8. Eran Segal

Citations in the corpus

• The Controversial Role of Human Gut Lachnospiraceae (2020, background): “In healthy conditions, bacteria will only exceptionally cross the mucus to specifically interact with epithelial cells [2].”
• Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations. (2016, positive): “We used segmented filamentous bacteria (SFB) indigenous to mice (mSFB) or rats (rSFB), previously shown to feature differential adherence to the intestinal epithelium (Atarashi et al., 2015).”
• Antibiotic-Induced Changes in the Intestinal Microbiota and Disease. (2016, background): “Physical interactions between SFB and enterocytes, to which the bacteria are tightly anchored, are required for the induction of Th17-polarizing molecules [serum amyloid A (SAA), IL-1b] [33,34].”
• Role of intestinal microbiota and metabolites on gut homeostasis and human diseases (2017, background): “illustrated that this preferential induction of IL-17 in Th17 cells might be attributed to intimate SFB attachment to the small intestine epithelium [123].”
• Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease (2017, background): “Consistently, mice lacking GPR43 have lower numbers of Tregs.”
• Understanding the Holobiont: How microbial metabolites affect human health and shape the immune system (2017, background): “The capability of other TH17-inducing gut bacteria to produce ATP has not been determined yet, but a common property appears to be their ability to adhere to the intestinal epithelium (Atarashi et al., 2015; Tan et al., 2016).”
• The IL-17 family of cytokines in health and disease (2019, background): “While SFB is not thought to be causative in pathogenesis of IBD or cancer, other microbes with similar IL-17-inducing activities, including Staphylococcus saprophyticus, Bifidobacterium adolescentis, and enterotoxigenic Bacteroides fragilis (ETBF), are thought to contribute to the disease process(At”
• Interaction between microbiota and immunity in health and disease (2020, background): “Induction of Th17 cells by SFB is enabled by their adhesion to epithelial cells.(36) A bacterial polysaccharide derived from the ubiquitous commensal Bacteroides fragilis directs the maturation of the developing immune system in mice, including correction of systemic T cell deficiencies and Th1/Th2 ”
• Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and CNS inflammation via the aryl hydrocarbon receptor (2016, positive): “Depending on the experimental model, pro-and anti-inflammatory effects of the commensal flora have been recently reported 57,58,14,15,59 highlighting the need to identify the molecular mechanisms by which the commensal flora regulates the immune response.”
• Homeostatic immunity and the microbiota (2017, positive): “For instance, SFB colonization can promote IL-22 production by ILC3 in an IL-23 dependent manner (Atarashi et al., 2015; Sano et al., 2015).”