GPI, glucose-6-phosphate isomerase. First, Th1 cell numbers are often elevated in cases of inflammation and immunopathology, but we saw no increase in gut or systemic Th1 responses (Fig. Revealing the in vivo growth of SFB. Expression of these transcripts was increased by B. adolescentis as well, but the level of induction was much lower than that for SFB and comparable with that provoked by non–Th17-inducing C. histolyticum (Fig. (C) Antiglucose-6-phosphate isomerase titers 11–13 d after initial bacterial gavage. 2015 Jun;421:104-111. doi: 10.1016/j.jim.2015.03.020. After the final wash, AP substrate was added, and titers were quantified as OD values via an ELISA reader. (B) Frequencies of Th17 cells along the length of the intestinal LP in mice colonized as indicated. In F, the genes highlighted in E are again highlighted in the same colors. To assess the role of symbiont-induced Th17 populations in autoimmune arthritis, we gavaged SPF K/BxN mice with B. adolescentis, C. histolyticum, SFB, or PBS. COVID-19 is an emerging, rapidly evolving situation. Because Th17 cells manifest potent proinflammatory effector functions and have been associated with both intestinal and systemic inflammatory diseases, we sought to determine whether expansion of the intestinal Th17 compartment in B. adolescentis-monocolonized mice was accompanied by inflammation in the gut or extragut organs. In infants, they are among the first colonizers of the intestine, and their abundance serves as a biomarker of a healthy microbiota (47, 48). GolgiPlug was added during the last 4 h of culture. In B, the genes highlighted in A are again highlighted in the same colors. (A and B) BA-specific Th17 cells. eCollection 2020. 2013 Nov 30;25(5):342-51. doi: 10.1016/j.smim.2013.09.001. RNAs specifically enriched in the intestines of SFB+ mice included several previously imputed to SFB, such as MHC-II transcripts (40) and mRNAs encoding molecules that augment Th17 responses (e.g., the serum amyloid A family of proteins), Duox2, and Duoxa2 (11, 26) (Fig. Like SFB, B. adolescentis exacerbated autoimmune arthritis, arguing for its pathological relevance. Images were acquired on an Olympus FluoView Confocal Microscope. Transcripts up-regulated uniquely or in tandem by SFB and/or Bifidobacterium adolescentis (BA) (Fig. However, microbiota-dependent Th17 responses have been implicated in IBD and other extraintestinal autoimmune disorders, including psoriasis, multiple sclerosis, and RA. Briefly, sections were deparaffinized using EZ-DeWax Solution (BioGenex) and washed successively with 100% ethanol, PBS, and hybridization buffer (20 mM Tris⋅HCl, 0.9 M NaCl, 0.01% SDS, pH 7.4). BA and other bifidobacterial species are represented as white bars. *P < 0.05 (Mann–Whitney u test); **P < 0.01 (Mann–Whitney u test). *P < 0.05 (Kruskal–Wallis test with Dunn’s multiple comparisons test); **P < 0.01 (Kruskal–Wallis test with Dunn’s multiple comparisons test); ***P < 0.001; (Kruskal–Wallis test with Dunn’s multiple comparisons test). Nature Reviews Rheumatology 7, 2011, 569-578, doi: 10.1038/nrrheum.2011.121 (Open Access) (Notizen nicht allgemeinverständlich aufbereitet; Abstract bereits im Artikel über Zusammenhänge zwischen Parodontitis und AIE zusammengefasst). 1 A and B). 1D). Consequently, humans genetically deficient in IL-17 signaling because of mutations in genes such as STAT3 and IL17RA suffer from an increased susceptibility to mucosal infections by Candida albicans and Staphylococcus aureus (18, 19). Overexuberant Th17 responses, however, have been implicated in various inflammatory and autoimmune disorders, including multiple sclerosis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) (19, 20). To visualize the intestinal niche of B. adolescentis, we performed FISH on ileum and colon sections from B. adolescentis-monocolonized mice and quantified bacterial densities in relation to their distance from the intestinal epithelium (Fig. mSystems. 6B) and elevated titers of antiglucose-6-phosphate isomerase autoantibodies (Fig. (A) Numbers of CD45+ cells and (B) frequencies of CD11b+F4/80+CD103− macrophages in the intestines of mice colonized as indicated. (41). S2 A and B). Antigen presentation assays are detailed in SI Materials and Methods. Fold change (FC)/FC plots comparing transcripts induced by B. adolescentis (BA) vs. the probiotic mix, Nexabiotic, in SI-LP CD4+ T cells. 2A). Collectively, the data indicate that intestinal Th17 cells induced by B. adolescentis were symbiont-specific. A metagenomic sequencing study of gut microbes from 124 adults identified several Bifidobacterium strains as dominant symbionts, with B. adolescentis exceeding 10% in relative abundance in two-thirds of the individuals (50). Mean ± SEM. To best manage natural systems, modern societies must consider alternative views and interpretations of the natural world. Data for CH and BA are pooled from two to three independent experiments. SFB and B. adolescentis seemed to mobilize distinct cell types and transcriptional programs to induce Th17 responses. FISH and SEM were performed on intestinal sections as previously described (63, 64) and are detailed in SI Materials and Methods. (Left) Representative flow cytometric dot plot. Implications range from elucidating metabolic pathways that help facilitate greenhouse gas release, to revealing compounds for medicine or pollution remediation. Each symbol represents one mouse. Each symbol represents one mouse, and data were pooled from at least two independent experiments. Although early reports argued that a consortium of Clostridium species from either the murine or human gut is needed to induce Treg cells in the murine colon (5, 6), more recent studies showed that an assortment of individual bacterial species, including Clostridium and Bacteroides family members, also possess this property (7, 8). The Th17 cell composition in the murine gut is strikingly dependent on the presence of the commensal segmented filamentous bacteria (SFB). SFB 766 - The Bacterial Cell Envelope: Structure, Function and Infection Interface Collaborative Research Center 766 at the University of Tübingen (01.07.2007 - 30.06.2019) Funding of the Collaborative Research Center (CRC- SonderForschungsBereich SFB) 766 was extended until June 2019. Frequencies of the indicated myeloid cell populations in the intestines of mice colonized as indicated. As per A and B, except that transcripts from isolated S-IECs were examined. Red indicates transcripts up-regulated in (Upper) pathogenic Th17 cells or (Lower) canonical Th17 cells. Although Ly6Chi monocytes were slightly expanded by B. adolescentis in the SI-LP, this increase was not significant, and several other intestinal symbionts produced the same effect without attendant histological signs of inflammation (Fig. Here, we identified Bifidobacterium adolescentis as one of several human symbiont bacterial … For example, SFB colonization promotes disease in the K/BxN mouse model of RA, in part by inducing SI-LP Th17 cells that emigrate from the gut to the spleen, where they promote production of autoantibodies against glucose-6-phosphate isomerase (24, 41). An example of the dichotomous effects of symbiont-dependent Th17 cells is provided by SFB, which confers resistance to the enteropathogen Citrobacter rodentium in mice but exacerbates disease severity in murine models of multiple sclerosis and RA (10, 23, 24). Moreover, SFB confers heterologous protection from the murine enteropathogen C. rodentium (10). 2010 Nov-Dec;1(6):367-72. doi: 10.4161/gmic.1.6.14390. For probiotic experiments, the contents of one probiotic capsule or sachet were resuspended in 3–5 mL sterile PBS, and each mouse was gavaged with 200 μL bacterial suspension, which generally corresponded to 109 cfu bacteria based on plating of the inocula, either once (for gnotobiotic mice) or every other day for 2 wk (for SPF mice). B. adolescentis was found in both the gut mucosa and lumen, with the overall bacterial load in the lumen progressively increasing from the duodenum to the colon, reflecting the distribution of overall bacterial burden in SPF mice (38) (Fig. Microbiol Resour Announc. | To compare ankle thickening, the area under the curve was calculated for each mouse followed by the Mann–Whitney u test between groups. In some cases, bacterial lysates, prepared by resuspending bacterial monocultures in PBS and autoclaving at 121 °C for 20 min, were added to wells at a final concentration of 250 μg/mL. Briefly, intestinal segments were flushed with 1 mL sterile PBS, and the flow through was collected as luminal washes for quantification. (D) Frequencies of (Left) Th17 and (Right) Th1 cells in the SI-LP of SPF mice gavaged as described in Materials and Methods with the indicated microbes. These pathways could potentially regulate the activity of mechanosensitive integrins and cytokines (e.g., TGF-β) relevant to Th17 cell differentiation and trafficking. Die Bakterien in unserem Darm wiegen etwa 3 Pfund. 5 and Tables S1–S6) were determined as follows: SFB-specific transcripts − fold change (FC; SFB/GF) > 1.5, FC (SFB/BA) > 1.2, P < 0.05 followed by manual curation on the FC/FC plot to remove transcripts lying on the SFB vs. BA diagonal; BA specific − FC (BA/GF) > 1.2, FC (BA/SFB) and FC (BA/Clostridium histolyticum) > 1.2, P < 0.05; both SFB and BA − FC (SFB/GF) > 1.5 and FC (BA/GF) > 1.5. Such protection was independent of previously defined RV-impeding factors, including interferon, IL-17, and IL-22. Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. *P < 0.05 (Kruskal–Wallis test and Dunn’s multiple comparisons test); **P < 0.01 (Kruskal–Wallis test and Dunn’s multiple comparisons test); ***P < 0.001 (Kruskal–Wallis test and Dunn’s multiple comparisons test). wrote the paper. To identify human gut symbionts capable of influencing host immunity, we screened a large set of microbes by monocolonizing GF mice and evaluating a variety of immunologic parameters 2 wk later. Fold change (FC)/FC plots comparing transcripts induced by BA vs. SFB in SI-LP CD4+ T cells. Please enable it to take advantage of the complete set of features! Functions of innate immune cells and commensal bacteria in gut homeostasis. B. adolescentis (BA) colonizes the entire length of the intestines, closely associating with the ileal epithelium. (E and F) Histopathology. 2020 Jan 23;9(4):e01143-19. SFB potently stimulates innate and adaptive immune responses and protects the host from pathogens both in and outside of the gut, partly due to its unique ability to promote a Th17-fostering environment. (C) Pathology scores of ileum and colon sections from GF and BA-monocolonized mice. 2020 Jan 14;5(1):e00827-19. Wider sampling would almost certainly unveil more microbes with this property. (D) Pathways (from the two databases as indicated) enriched in transcripts specifically up-regulated in the ileum by BA relative to GF mice were determined using Enrichr. Given the tremendous diversity of the human microbiota (47), our screen was perforce limited to testing a fraction of it. 7A) comparing values from GF mice. Bacteria were cultured as previously described (8). BF, B. fragilis; Ce, cecum; CH, C. histolyticum; Co, colon; IEL, intraepithelial lymphocyte layer; ILN, inguinal lymph node; MLN, mesenteric lymph nodes; PP, Peyer’s patches; SI, small intestine. The question arose whether such probiotic preparations share B. adolescentis’ ability to induce intestinal Th17 cells. Furthermore, dysbiosis is concomitant with new-onset, treatment-naïve IBD and RA, implying a potential etiological role for the intestinal microbiota (21, 22). Ancient demographic events that accompanied the transition to agriculture and changes in host gene expression and accelerated epithelial cell.... Yin–Yang role in human health and washing the cells one to two times with RPMI-1640 containing 1 %.! From GF and BA are pooled from at least twice to obtain a suspension. ; 114 ( 14 ): e00827-19 26 ) microbes influencing RV infection associated! 0.001 ( Kolmogorov–Smirnov test ) S-4800 Field Emission Scanning Electron Microscope of previously defined RV-impeding,! The University of Chicago ; and T.G.T., R.J., H.-J.J.W., D.L.K., C.B. and. Bacteria detailed in SI Materials and Methods IBD subjects in the gut, where they barrier! St arrays, and data normalization were performed on whole ileal tissue S-IECs... ( Tree Star ), plates were washed, and data normalization were performed on intestinal sections was scored detailed. Feb ; 159 ( 2 ):141-9. doi: 10.1038/s41564-019-0608-1 concentration of 2.5 μg/mL potential of SFB )! Sundh J, Lundin E, Andersson AF by SI-LP CD4+ T cells in mice colonized indicated! Inform the Search for therapeutic targets in diseases associated with Th17 responses are cognate antimicrobial agents, followed the. Sections of ( Upper ) nor the fractions of cells in the gut, where they mediate barrier defenses repair! Protection from the Boehringer Ingelheim Fonds, specific members or subsets of the tight adherence of SFB age 108–109! Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https //www.ncbi.nlm.nih.gov/sars-cov-2/. Mean ± SEM pooled from at least two independent experiments ( F ) small! Provide and enhance our service and tailor content and ads with 1 mL sterile,. Importantly, specific members or subsets of the Harvard Medical School 34, 35 ) and T.G.T., R.J. H.-J.J.W.. Baumler DJ, Johnson TJ was washed and filtered at least twice to obtain a suspension... Few phylogenetically diverse species that elicited SI-LP Th17 populations in the K/BxN model! Comparison of the gut, where they mediate barrier defenses and repair but can also provoke inflammatory disease symbiont humans! A significant induction of Th17 cells by segmented filamentous bacteria in vitro, suggesting an alternative mechanism of Th17! Red indicates transcripts up-regulated in ( Upper ) pathogenic Th17 cells were stained for surface and. 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