10 results on '"Galvez, Eric J. C."'
Search Results
2. Induction of IL-22-Producing CD4+ T Cells by Segmented Filamentous Bacteria Independent of Classical Th17 Cells
- Author
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Roy, Urmi, primary, de Oliveira, Rômulo S., additional, Galvez, Eric J. C., additional, Gronow, Achim, additional, Basic, Marijana, additional, Perez, Laura Garcia, additional, Gagliani, Nicola, additional, Bleich, Andre, additional, Huber, Samuel, additional, and Strowig, Till, additional
- Published
- 2021
- Full Text
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3. IL-17 controls central nervous system autoimmunity through the intestinal microbiome
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Regen, Tommy, Isaac, Sandrine, Amorim, Ana, Nunez, Nicolas Gonzalo, Hauptmann, Judith, Shanmugavadivu, Arthi, Klein, Matthias, Sankowski, Roman, Mufazalov, Ilgiz A., Yogev, Nir, Huppert, Jula, Wanke, Florian, Witting, Michael, Grill, Alexandra, Galvez, Eric J. C., Nikolaev, Alexei, Blanfeld, Michaela, Prinz, Immo, Schmitt-Kopplin, Philippe, Strowig, Till, Reinhardt, Christoph, Prinz, Marco, Bopp, Tobias, Becher, Burkhard, Ubeda, Carles, Waisman, Ari, Regen, Tommy, Isaac, Sandrine, Amorim, Ana, Nunez, Nicolas Gonzalo, Hauptmann, Judith, Shanmugavadivu, Arthi, Klein, Matthias, Sankowski, Roman, Mufazalov, Ilgiz A., Yogev, Nir, Huppert, Jula, Wanke, Florian, Witting, Michael, Grill, Alexandra, Galvez, Eric J. C., Nikolaev, Alexei, Blanfeld, Michaela, Prinz, Immo, Schmitt-Kopplin, Philippe, Strowig, Till, Reinhardt, Christoph, Prinz, Marco, Bopp, Tobias, Becher, Burkhard, Ubeda, Carles, and Waisman, Ari
- Abstract
Interleukin-17A- (IL-17A) and IL-17F-producing CD4(+) T helper cells (T(H)17 cells) are implicated in the development of chronic inflammatory diseases, such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). T-H 17 cells also orchestrate leukocyte invasion of the central nervous system (CNS) and subsequent tissue damage. However, the role of IL-17A and IL-17F as effector cytokines is still confused with the encephalitogenic function of the cells that produce these cytokines, namely, T-H 17 cells, fueling a long-standing debate in the neuroimmunology field. Here, we demonstrated that mice deficient for IL-17A/F lose their susceptibility to EAE, which correlated with an altered composition of their gut microbiota. However, loss of IL-17A/F in T-H cells did not diminish their encephalitogenic capacity. Reconstitution of a wild-type-like intestinal microbiota or reintroduction of IL-17A specifically into the gut epithelium of IL-17A/F-deficient mice reestablished their susceptibility to EAE. Thus, our data demonstrated that IL-17A and IL-17F are not encephalitogenic mediators but rather modulators of intestinal homeostasis that indirectly alter CNS-directed autoimmunity.
- Published
- 2021
4. Bridge helix arginines play a critical role in Cas9 sensitivity to mismatches
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Bratovic, Majda, Fonfara, Ines, Chylinski, Krzysztof, Galvez, Eric J. C., Sullivan, Timothy J., Boerno, Stefan, Timmermann, Bernd, Boettcher, Michael, Charpentier, Emmanuelle, Bratovic, Majda, Fonfara, Ines, Chylinski, Krzysztof, Galvez, Eric J. C., Sullivan, Timothy J., Boerno, Stefan, Timmermann, Bernd, Boettcher, Michael, and Charpentier, Emmanuelle
- Abstract
The RNA-programmable DNA-endonuclease Cas9 is widely used for genome engineering, where a high degree of specificity is required. To investigate which features of Cas9 determine the sensitivity to mismatches along the target DNA, we performed in vitro biochemical assays and bacterial survival assays in Escherichia coli. We demonstrate that arginines in the Cas9 bridge helix influence guide RNA, and target DNA binding and cleavage. They cluster in two groups that either increase or decrease the Cas9 sensitivity to mismatches. We show that the bridge helix is essential for R-loop formation and that R63 and R66 reduce Cas9 specificity by stabilizing the R-loop in the presence of mismatches. Additionally, we identify Q768 that reduces sensitivity of Cas9 to protospacer adjacent motif-distal mismatches. The Cas9_R63A/Q768A variant showed increased specificity in human cells. Our results provide a firm basis for function- and structure-guided mutagenesis to increase Cas9 specificity for genome engineering. Tuning CRISPR-Cas9 nuclease specificity enables precision genome engineering. Identifying arginine residues along the bridge helix of SpCas9 that mediate Cas9 mismatch sensitivity enabled engineering of Cas9 with increased specificity in human cells.
- Published
- 2020
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- View/download PDF
5. Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis
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Liao, Lijun, primary, Schneider, Kai Markus, additional, Galvez, Eric J C, additional, Frissen, Mick, additional, Marschall, Hanns-Ulrich, additional, Su, Huan, additional, Hatting, Maximilian, additional, Wahlström, Annika, additional, Haybaeck, Johannes, additional, Puchas, Philip, additional, Mohs, Antje, additional, Peng, Jin, additional, Bergheim, Ina, additional, Nier, Anika, additional, Hennings, Julia, additional, Reißing, Johanna, additional, Zimmermann, Henning W, additional, Longerich, Thomas, additional, Strowig, Till, additional, Liedtke, Christian, additional, Cubero, Francisco J, additional, and Trautwein, Christian, additional
- Published
- 2019
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6. Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis.
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Lijun Liao, Schneider, Kai Markus, Galvez, Eric J. C., Frissen, Mick, Marschall, Hanns-Ulrich, Huan Su, Hatting, Maximilian, Wahlström, Annika, Haybaeck, Johannes, Puchas, Philip, Mohs, Antje, Jin Peng, Bergheim, Ina, Nier, Anika, Hennings, Julia, Reißing, Johanna, Zimmermann, Henning W., Longerich, Thomas, Strowig, Till, and Liedtke, Christian
- Subjects
NLRP3 protein ,LIVER diseases ,DISEASE progression ,CHOLANGITIS - Published
- 2019
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7. Helicobacter spp. are prevalent in wild mice and protect from lethal Citrobacter rodentium infection in the absence of adaptive immunity.
- Author
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Zhao B, Osbelt L, Lesker TR, Wende M, Galvez EJC, Hönicke L, Bublitz A, Greweling-Pils MC, Grassl GA, Neumann-Schaal M, and Strowig T
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- Animals, Mice, Citrobacter rodentium, Adaptive Immunity, Mice, Inbred C57BL, Enterobacteriaceae Infections, Microbiota, Gastrointestinal Microbiome
- Abstract
Transfer of the gut microbiota from wild to laboratory mice alters the host's immune status and enhances resistance to infectious and metabolic diseases, but understanding of which microbes and how they promote host fitness is only emerging. Our analysis of metagenomic sequencing data reveals that Helicobacter spp. are enriched in wild compared with specific-pathogen-free (SPF) and conventionally housed mice, with multiple species commonly co-colonizing their hosts. We create laboratory mice harboring three non-SPF Helicobacter spp. to evaluate their effect on mucosal immunity and colonization resistance to the enteropathogen Citrobacter rodentium. Our experiments reveal that Helicobacter spp. interfere with C. rodentium colonization and attenuate C. rodentium-induced gut inflammation in wild-type (WT) mice, even preventing lethal infection in Rag2
-/- SPF mice. Further analyses suggest that Helicobacter spp. interfere with tissue attachment of C. rodentium, putatively by reducing the availability of mucus-derived sugars. These results unveil pivotal protective functions of wild mouse microbiota constituents against intestinal infection., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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8. Klebsiella oxytoca causes colonization resistance against multidrug-resistant K. pneumoniae in the gut via cooperative carbohydrate competition.
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Osbelt L, Wende M, Almási É, Derksen E, Muthukumarasamy U, Lesker TR, Galvez EJC, Pils MC, Schalk E, Chhatwal P, Färber J, Neumann-Schaal M, Fischer T, Schlüter D, and Strowig T
- Subjects
- Adaptive Immunity, Adult, Animals, Bacterial Proteins genetics, Bacterial Proteins metabolism, Child, Drug Resistance, Multiple, Bacterial, Gastrointestinal Microbiome, Germ-Free Life, Glucosides metabolism, Humans, Klebsiella Infections immunology, Klebsiella Infections microbiology, Klebsiella oxytoca genetics, Klebsiella oxytoca isolation & purification, Klebsiella pneumoniae drug effects, Mice, Mice, Inbred C57BL, Carbohydrate Metabolism, Feces microbiology, Gastrointestinal Tract microbiology, Klebsiella oxytoca physiology, Klebsiella pneumoniae growth & development, Microbial Interactions
- Abstract
Gut colonization with multidrug-resistant (MDR) bacteria enhances the risk of bloodstream infections in susceptible individuals. We demonstrate highly variable degrees of ex vivo colonization resistance against a carbapenem-resistant Klebsiella pneumoniae strain in human feces samples and subsequently isolate diverse K. oxytoca strains from protected donors. Several of these K. oxytoca strains reduce gut colonization of MDR K. pneumoniae strains in antibiotic-treated and gnotobiotic mouse models. Comparative analysis of K. oxytoca strains coupled with CRISPR-Cas9-mediated deletion of casA, a protein essential for utilization of selected beta-glucosides, identified competition for specific carbohydrates as key in promoting colonization resistance. In addition to direct competition between K. oxytoca and K. pneumoniae, cooperation with additional commensals is required to reestablish full colonization resistance and gut decolonization. Finally, humanized microbiota mice generated from K. pneumoniae-susceptible donors are protected by K. oxytoca administration, demonstrating the potential of commensal K. oxytoca strains as next-generation probiotics., Competing Interests: Declaration of interests A patent for the use of K. oxytoca to decolonize MDR Enterobacteriaceae from the gut has been filed (EP 20212877.3)., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
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9. Modulation of inflammatory responses by gastrointestinal Prevotella spp. - From associations to functional studies.
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Iljazovic A, Amend L, Galvez EJC, de Oliveira R, and Strowig T
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- Gastrointestinal Tract, Humans, Intestines, Dysbiosis, Gastrointestinal Microbiome, Host Microbial Interactions, Inflammation microbiology, Prevotella metabolism
- Abstract
Numerous studies have associated alterations in the gut microbiota composition with almost every known inflammatory disease. However, proving the biological relevance of distinct microbial signatures and linking specific microorganisms to host phenotypes, remains a considerable challenge. Correspondingly, increased abundance of members of Prevotella genus within microbial communities colonizing distinct mucosal surfaces has been found in individuals diagnosed with rheumatoid arthritis, periodontitis, metabolic disorders, and intestinal and vaginal dysbiosis. Still, the role of Prevotella spp. in the incidence of these diseases continues to be debated. For many years, poor understanding of Prevotella biology could be in large part attributed to the lack of experimental tools. However, in the recent years significant advances have been made towards overcoming these limitations, including increased number of isolates and improved understanding of genetic diversity. Besides discussing the most relevant associations between Prevotella spp. and inflammatory disorders, in the present review we examine the recent efforts to expand the Prevotella experimental "toolbox" and we highlight remaining experimental challenges that should advance future research and our understanding of Prevotella-host interplay., (Copyright © 2021. Published by Elsevier GmbH.)
- Published
- 2021
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10. Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury.
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Schneider KM, Elfers C, Ghallab A, Schneider CV, Galvez EJC, Mohs A, Gui W, Candels LS, Wirtz TH, Zuehlke S, Spiteller M, Myllys M, Roulet A, Ouzerdine A, Lelouvier B, Kilic K, Liao L, Nier A, Latz E, Bergheim I, Thaiss CA, Hengstler JG, Strowig T, and Trautwein C
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- Analgesics, Non-Narcotic toxicity, Animals, Chemical and Drug Induced Liver Injury etiology, Female, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Permeability, Acetaminophen toxicity, Chemical and Drug Induced Liver Injury pathology, Disease Models, Animal, Dysbiosis complications, Gastrointestinal Microbiome, Receptors, Cell Surface physiology
- Abstract
Background & Aims: Acute liver failure (ALF) represents an unmet medical need in Western countries. Although the link between intestinal dysbiosis and chronic liver disease is well-established, there is little evidence for a functional role of gut-liver interaction during ALF. Here we hypothesized that intestinal dysbiosis may affect ALF., Methods: To test this hypothesis, we assessed the association of proton pump inhibitor (PPI) or long-term antibiotics (ABx) intake, which have both been linked to intestinal dysbiosis, and occurrence of ALF in the 500,000 participants of the UK BioBank population-based cohort. For functional studies, male Nlrp6
-/- mice were used as a dysbiotic mouse model and injected with a sublethal dose of acetaminophen (APAP) or lipopolysaccharide (LPS) to induce ALF., Results: Multivariate Cox regression analyses revealed a significantly increased risk (odds ratio, 2.3-3) for developing ALF in UK BioBank participants with PPI or ABx. Similarly, dysbiotic Nlrp6-/- mice displayed exacerbated APAP- and LPS-induced liver injury, which was linked to significantly reduced gut and liver tissue microbiota diversity and correlated with increased intestinal permeability at baseline. Fecal microbiota transfer (FMT) from Nlrp6-/- mice into wild-type (WT) mice augmented liver injury on APAP treatment in recipient WT mice, resembling the inflammatory phenotype of Nlrp6-/- mice. Specifically, FMT skewed monocyte polarization in WT mice toward a Ly6Chi inflammatory phenotype, suggesting a critical function of these cells as sensors of gut-derived signals orchestrating the inflammatory response., Conclusions: Our data show an important yet unknown function of intestinal microbiota during ALF. Intestinal dysbiosis was transferrable to healthy WT mice via FMT and aggravated liver injury. Our study highlights intestinal microbiota as a targetable risk factor for ALF., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
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