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Article ; Online: Evading the Toll booth: How "silent" flagellins may bind yet fail to activate TLR5.

Baer, Hannah M / Sandilya, Shruti / Steiner, Theodore S

Science immunology

2023 Volume 8, Issue 79, Page(s) eadf0244

Abstract: The nature of flagellin-Toll-like receptor 5 (TLR5) interactions, depending on binding to and activation of TLR5, may hold a key to the distinct differences in gut microbiome and intestinal immune function in different populations around the world (see ... ...

Abstract	The nature of flagellin-Toll-like receptor 5 (TLR5) interactions, depending on binding to and activation of TLR5, may hold a key to the distinct differences in gut microbiome and intestinal immune function in different populations around the world (see related Research Article by Clasen
MeSH term(s)	Toll-Like Receptor 5 ; Flagellin/metabolism ; Intestines
Chemical Substances	Toll-Like Receptor 5 ; Flagellin (12777-81-0)
Language	English
Publishing date	2023-01-06
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Comment
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.adf0244
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Article ; Online: Clostridioides difficile PCR Tcdb Cycle Threshold predicts toxin EIA positivity but not severity of infection.

Mah, Regan / Locher, Kerstin / Steiner, Theodore S / Stefanovic, Aleksandra

Anaerobe

2023 Volume 82, Page(s) 102755

Abstract: Background: Diagnosis of Clostridioides difficile Infection (CDI) entails compatible clinical presentation and laboratory findings. We evaluated real-time polymerase chain reaction (qPCR) cycle threshold (C: Methods: Inpatients or emergency ... ...

Abstract	Background: Diagnosis of Clostridioides difficile Infection (CDI) entails compatible clinical presentation and laboratory findings. We evaluated real-time polymerase chain reaction (qPCR) cycle threshold (C Methods: Inpatients or emergency department patients who tested positive for tcdB gene by PCR were evaluated. Patients' stools underwent testing for GDH and TcdA/B by EIA. Medical health records were reviewed for demographic, clinical presentation, laboratory, treatment and outcome data. Severity of CDI was calculated using various severity score indexes. Results: The median C Conclusion: C
MeSH term(s)	Humans ; Bacterial Toxins/genetics ; Bacterial Toxins/analysis ; Clostridioides difficile/genetics ; Clostridioides/genetics ; Immunoenzyme Techniques ; Clostridium Infections/diagnosis ; Real-Time Polymerase Chain Reaction ; Feces/chemistry ; Bacterial Proteins/genetics ; Bacterial Proteins/analysis
Chemical Substances	Bacterial Toxins ; Bacterial Proteins
Language	English
Publishing date	2023-07-03
Publishing country	England
Document type	Journal Article
ZDB-ID	1237621-8
ISSN	1095-8274 ; 1075-9964
ISSN (online)	1095-8274
ISSN	1075-9964
DOI	10.1016/j.anaerobe.2023.102755
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Article ; Online: New Insights Into Shiga Toxigenic Escherichia coli Pathogenesis: When Less Is More.

Steiner, Theodore S

The Journal of infectious diseases

2016 Volume 213, Issue 8, Page(s) 1214–1215

MeSH term(s)	Animals ; Female ; Shiga Toxin 1/pharmacokinetics ; Shiga Toxin 1/toxicity ; Shiga Toxin 2/antagonists & inhibitors ; Shiga Toxin 2/toxicity
Chemical Substances	Shiga Toxin 1 ; Shiga Toxin 2
Language	English
Publishing date	2016-04-15
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiv558
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Article ; Online: T-cell activation-induced marker assays in health and disease.

Poloni, Chad / Schonhofer, Cole / Ivison, Sabine / Levings, Megan K / Steiner, Theodore S / Cook, Laura

Immunology and cell biology

2023 Volume 101, Issue 6, Page(s) 491–503

Abstract: Activation-induced marker (AIM) assays have proven to be an accessible and rapid means of antigen-specific T-cell detection. The method typically involves short-term incubation of whole blood or peripheral blood mononuclear cells with antigens of ... ...

Abstract	Activation-induced marker (AIM) assays have proven to be an accessible and rapid means of antigen-specific T-cell detection. The method typically involves short-term incubation of whole blood or peripheral blood mononuclear cells with antigens of interest, where autologous antigen-presenting cells process and present peptides in complex with major histocompatibility complex (MHC) molecules. Recognition of peptide-MHC complexes by T-cell receptors then induces upregulation of activation markers on the T cells that can be detected by flow cytometry. In this review, we highlight the most widely used activation markers for assays in the literature while identifying nuances and potential downfalls associated with the technique. We provide a summary of how AIM assays have been used in both discovery science and clinical studies, including studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity. This review primarily focuses on AIM assays using human blood or peripheral blood mononuclear cell samples, with some considerations noted for tissue-derived T cells and nonhuman samples. AIM assays are a powerful tool that enables detailed analysis of antigen-specific T-cell frequency, phenotype and function without needing to know the precise antigenic peptides and their MHC restriction elements, enabling a wider analysis of immunity generated following infection and/or vaccination.
MeSH term(s)	Humans ; Leukocytes, Mononuclear ; COVID-19 ; SARS-CoV-2 ; T-Lymphocytes ; Peptides ; Antigens
Chemical Substances	Peptides ; Antigens
Language	English
Publishing date	2023-03-21
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1111/imcb.12636
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Article ; Online: The worst of both worlds: examining the hypervirulence of the shigatoxigenic/enteroaggregative Escherichia coli O104:H4.

Steiner, Theodore S

The Journal of infectious diseases

2014 Volume 210, Issue 12, Page(s) 1860–1862

MeSH term(s)	Epithelial Cells/metabolism ; Escherichia coli/metabolism ; Humans ; Protein Transport ; Shiga Toxin 2/metabolism
Chemical Substances	Shiga Toxin 2
Language	English
Publishing date	2014-12-15
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiu400
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Article ; Online: Clostridioides difficile PCR Tcdb Cycle Threshold predicts toxin EIA positivity but not severity of infection

Mah, Regan / Locher, Kerstin / Steiner, Theodore S. / Stefanovic, Aleksandra

Anaerobe. 2023 Aug., v. 82 p.102755-

2023

Abstract: Diagnosis of Clostridioides difficile Infection (CDI) entails compatible clinical presentation and laboratory findings. We evaluated real-time polymerase chain reaction (qPCR) cycle threshold (CT) as a predictor for disease severity and TcdB enzyme ... ...

Abstract	Diagnosis of Clostridioides difficile Infection (CDI) entails compatible clinical presentation and laboratory findings. We evaluated real-time polymerase chain reaction (qPCR) cycle threshold (CT) as a predictor for disease severity and TcdB enzyme immunoassay (EIA) results. Inpatients or emergency department patients who tested positive for tcdB gene by PCR were evaluated. Patients’ stools underwent testing for GDH and TcdA/B by EIA. Medical health records were reviewed for demographic, clinical presentation, laboratory, treatment and outcome data. Severity of CDI was calculated using various severity score indexes. The median CT of cases was 32.05 ± 5.45. The optimal cut-off for predicting toxin EIA positivity and severe CDI based on chart review was 32.6 and 29.8, respectively, with the area under the receiver operator characteristics curve (AUC) of 0.74 and 0.60 respectively. CT value was an acceptable predictor for EIA toxin but less so for clinical severity. Our study potentially supports a diagnostic algorithm including CT value to reduce the number of EIA toxin assays performed.
Keywords	Clostridium difficile ; algorithms ; disease severity ; enzyme immunoassays ; genes ; quantitative polymerase chain reaction ; toxins ; Clostridioides difficile ; Cycle_threshold ; Polymerase_chain_reaction ; EIA_Toxin
Language	English
Dates of publication	2023-08
Publishing place	Elsevier Ltd
Document type	Article ; Online
ZDB-ID	1237621-8
ISSN	1075-9964
ISSN	1075-9964
DOI	10.1016/j.anaerobe.2023.102755
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Altered receptor binding, antibody evasion and retention of T cell recognition by the SARS-CoV-2 XBB.1.5 spike protein.

Mannar, Dhiraj / Saville, James W / Poloni, Chad / Zhu, Xing / Bezeruk, Alison / Tidey, Keith / Ahmed, Sana / Tuttle, Katharine S / Vahdatihassani, Faezeh / Cholak, Spencer / Cook, Laura / Steiner, Theodore S / Subramaniam, Sriram

Nature communications

2024 Volume 15, Issue 1, Page(s) 1854

Abstract: The XBB.1.5 variant of SARS-CoV-2 has rapidly achieved global dominance and exhibits a high growth advantage over previous variants. Preliminary reports suggest that the success of XBB.1.5 stems from mutations within its spike glycoprotein, causing ... ...

Abstract	The XBB.1.5 variant of SARS-CoV-2 has rapidly achieved global dominance and exhibits a high growth advantage over previous variants. Preliminary reports suggest that the success of XBB.1.5 stems from mutations within its spike glycoprotein, causing immune evasion and enhanced receptor binding. We present receptor binding studies that demonstrate retention of binding contacts with the human ACE2 receptor and a striking decrease in binding to mouse ACE2 due to the revertant R493Q mutation. Despite extensive evasion of antibody binding, we highlight a region on the XBB.1.5 spike protein receptor binding domain (RBD) that is recognized by serum antibodies from a donor with hybrid immunity, collected prior to the emergence of the XBB.1.5 variant. T cell assays reveal high frequencies of XBB.1.5 spike-specific CD4
MeSH term(s)	Humans ; Animals ; Mice ; SARS-CoV-2/genetics ; CD8-Positive T-Lymphocytes ; Angiotensin-Converting Enzyme 2 ; Spike Glycoprotein, Coronavirus/genetics ; COVID-19 ; Antibodies
Chemical Substances	spike protein, SARS-CoV-2 ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Spike Glycoprotein, Coronavirus ; Antibodies
Language	English
Publishing date	2024-02-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-46104-2
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Article ; Online: Adaptive immune response to Clostridium difficile infection: A perspective for prevention and therapy.

Rees, William D / Steiner, Theodore S

European journal of immunology

2018 Volume 48, Issue 3, Page(s) 398–406

Abstract: Clostridium difficile infection (CDI) is one of the most important nosocomial illnesses and a major cause of morbidity and mortality. While initial treatment of CDI is usually successful, unprovoked relapses remain an important and frustrating problem. ... ...

Abstract	Clostridium difficile infection (CDI) is one of the most important nosocomial illnesses and a major cause of morbidity and mortality. While initial treatment of CDI is usually successful, unprovoked relapses remain an important and frustrating problem. This review examines the literature describing the natural immune response to CDI, and to what extent it can explain the propensity for relapses. In particular, we discuss studies on antibody and, to a lesser extent, B cell and T cell responses in CDI. Despite years of study, there remains incomplete understanding of the natural antibody response to the major pathogenic toxins, TcdA and TcdB, and other bacterial antigens, in CDI. Recent literature suggests that a specific subset of neutralizing antibodies that target the putative carbohydrate-binding domains of TcdB and possibly TcdA have the greatest protective ability. This is further supported by recent successful clinical trials of a humanized monoclonal antibody to the major toxin TcdB. A better understanding of how and why the most protective adaptive immune response develops may lead to improved vaccine and therapeutic targets for recurrent CDI.
MeSH term(s)	Adaptive Immunity ; Animals ; Antibodies, Bacterial/immunology ; Antibodies, Neutralizing/immunology ; B-Lymphocytes/immunology ; Bacterial Proteins/immunology ; Bacterial Toxins/immunology ; Carrier State/immunology ; Clostridium Infections/immunology ; Clostridium Infections/therapy ; Disease Models, Animal ; Enterotoxins/immunology ; Humans ; Immunologic Memory ; Immunotherapy ; Mice ; Recurrence ; Secondary Prevention ; T-Lymphocytes/immunology ; Vaccination
Chemical Substances	Antibodies, Bacterial ; Antibodies, Neutralizing ; Bacterial Proteins ; Bacterial Toxins ; Enterotoxins ; tcdA protein, Clostridium difficile ; toxB protein, Clostridium difficile
Language	English
Publishing date	2018-01-19
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.201747295
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Zs.A 489: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Patients' Willingness and Perspectives Toward Chimeric Antigen Receptor T-Regulatory Cell Therapy for Inflammatory Bowel Diseases.

Vent-Schmidt, Jens / Goldsmith, Laurie J / Steiner, Theodore S

Crohn's & colitis 360

2020 Volume 2, Issue 4, Page(s) otaa085

Abstract: Background: Inflammatory bowel disease is a life-changing disease resulting from recurrent intestinal inflammation. Current therapies (eg, steroids and biologics) are associated with mild to severe side effects, and none provide a cure. Recent research ... ...

Abstract	Background: Inflammatory bowel disease is a life-changing disease resulting from recurrent intestinal inflammation. Current therapies (eg, steroids and biologics) are associated with mild to severe side effects, and none provide a cure. Recent research has focused on genetically engineering gut-specific anti-inflammatory T-regulatory cells (CAR-Tregs) to control intestinal inflammation, a logistically and conceptually complex approach. The purpose of our study was to understand patients' willingness to try CAR-Treg given 2 hypothetical scenarios-in a clinical trial or as a new treatment. Methods: We surveyed people living with inflammatory bowel disease about their willingness to try CAR-Treg. The online survey was developed using patient focus groups and associated literature. We recruited participants through email and social media. We used descriptive and inferential statistics to analyze closed-ended questions and inductive thematic analysis to analyze open-ended follow-up questions. Results: Survey participants indicated high willingness to try CAR-Treg therapy in both a clinical trial and as a new treatment. Willingness to try was not correlated with disease state or medication history. Women were less likely than men to indicate willingness to participate in a clinical trial. Participants' reasons for being willing to try CAR-Treg therapy included the wish to change their current treatment and the calling to participate in research. Participants that were not willing to try CAR-Treg mentioned the lack of long-term data and the success of their current therapy. Conclusions: This is the first study to our knowledge to investigate patient willingness to try CAR-Treg therapy. Our results demonstrate the promise of moving this therapy into clinical practice as most patients indicated willingness to try.
Language	English
Publishing date	2020-10-21
Publishing country	England
Document type	Journal Article
ISSN	2631-827X
ISSN (online)	2631-827X
DOI	10.1093/crocol/otaa085
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Article ; Online: How do immune and mesenchymal cells influence the intestinal epithelial cell compartment in inflammatory bowel disease? Let's crosstalk about it!

Rees, William D / Sly, Laura M / Steiner, Theodore S

Journal of leukocyte biology

2020 Volume 108, Issue 1, Page(s) 309–321

Abstract: Intestinal epithelial cells provide a front line of defense by establishing a barrier against food Ags, pathogens, and commensal microorganisms. This defense includes the establishment of a tolerogenic environment in the gastrointestinal (GI) tract. The ... ...

Abstract	Intestinal epithelial cells provide a front line of defense by establishing a barrier against food Ags, pathogens, and commensal microorganisms. This defense includes the establishment of a tolerogenic environment in the gastrointestinal (GI) tract. The intestinal epithelium replenishes itself by cell turnover every 4-5 days, and this process is facilitated by various pathways of communication between the intestinal epithelial cells (IECs), the underlying stromal cell network, and professional immune cells, which together help establish a proper intestinal stem cell (ISC) niche in the crypt. However, during a state of inflammation, such as in inflammatory bowel diseases (IBD), these communication pathways can be altered, and this can lead to the development of inflammatory IECs within the crypt that further drive inflammation. Here, we review the current literature looking at crosstalk between immune cells, stromal cells, and IECs: how does the immune system potentially alter the ISC niche, and how do IECs influence intestinal immunity? We discuss the latest research using single cell RNA sequencing and intestinal organoid cultures to help answer these questions. A better understanding of this complex crosstalk can help lead to a better understanding of intestinal biology in general, and more efficient therapeutic approaches to treat IBD.
MeSH term(s)	Animals ; Cell Compartmentation/immunology ; Epithelial Cells/immunology ; Humans ; Inflammatory Bowel Diseases/immunology ; Intestines/pathology ; Leukocytes/immunology ; Mesenchymal Stem Cells/immunology
Language	English
Publishing date	2020-02-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1002/JLB.3MIR0120-567R
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