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Article ; Online: Transient IgA, steady IgG?

Berthold, Dorothée L / Wormald, Catherine

2020 Volume 20, Issue 8, Page(s) 462

Keywords	covid19
Language	English
Publishing date	2020-06-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2062776-2
ISSN	1474-1741 ; 1474-1733
ISSN (online)	1474-1741
ISSN	1474-1733
DOI	10.1038/s41577-020-0382-6
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Zs.A 5565: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Regional specialization of macrophages along the gastrointestinal tract.

Berthold, Dorothée L / Jones, Kelsey D J / Udalova, Irina A

Trends in immunology

2021 Volume 42, Issue 9, Page(s) 795–806

Abstract: The tissue microenvironment is a major driver in imprinting tissue-specific macrophage functions in various mammalian tissues. As monocytes are recruited into the gastrointestinal (GI) tract at steady state and inflammation, they rapidly adopt a tissue- ... ...

Abstract	The tissue microenvironment is a major driver in imprinting tissue-specific macrophage functions in various mammalian tissues. As monocytes are recruited into the gastrointestinal (GI) tract at steady state and inflammation, they rapidly adopt a tissue-specific and distinct transcriptome. However, the GI tract varies significantly along its length, yet most studies of intestinal macrophages do not directly compare the phenotype and function of these macrophages in the small and large intestine, thus leading to disparities in data interpretations. This review highlights differences along the GI tract that are likely to influence macrophage function, with a specific focus on diet and microbiota. This analysis may fuel further investigation regarding the interplay between the intestinal immune system and GI tissue microenvironments, ideally providing unique therapeutic targets to modulate specific intestinal macrophage populations and/or functions.
MeSH term(s)	Animals ; Gastrointestinal Tract ; Intestines ; Macrophages ; Microbiota ; Monocytes
Language	English
Publishing date	2021-08-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2021.07.006
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Zs.A 1601: 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: Macrophages in the synovial lining niche initiate neutrophil recruitment and articular inflammation.

Zec, Kristina / Schonfeldova, Barbora / Ai, Zhichao / Van Grinsven, Erinke / Pirgova, Gabriela / Eames, Hayley L / Berthold, Dorothée L / Attar, Moustafa / Compeer, Ewoud B / Arnon, Tal I / Udalova, Irina A

The Journal of experimental medicine

2023 Volume 220, Issue 8

Abstract: The first immune-activating changes within joint resident cells that lead to pathogenic leukocyte recruitment during articular inflammation remain largely unknown. In this study, we employ state-of-the-art confocal microscopy and image analysis in a ... ...

Abstract	The first immune-activating changes within joint resident cells that lead to pathogenic leukocyte recruitment during articular inflammation remain largely unknown. In this study, we employ state-of-the-art confocal microscopy and image analysis in a systemic, whole-organ, and quantitative way to present evidence that synovial inflammation begins with the activation of lining macrophages. We show that lining, but not sublining macrophages phagocytose immune complexes containing the model antigen. Using the antigen-induced arthritis (AIA) model, we demonstrate that on recognition of antigen-antibody complexes, lining macrophages undergo significant activation, which is dependent on interferon regulatory factor 5 (IRF5), and produce chemokines, most notably CXCL1. Consequently, at the onset of inflammation, neutrophils are preferentially recruited in the vicinity of antigen-laden macrophages in the synovial lining niche. As inflammation progresses, neutrophils disperse across the whole synovium and form swarms in synovial sublining during resolution. Our study alters the paradigm of lining macrophages as immunosuppressive cells to important instigators of synovial inflammation.
MeSH term(s)	Humans ; Neutrophil Infiltration ; Arthritis/pathology ; Macrophages ; Synovial Membrane/pathology ; Inflammation/pathology ; Antigens
Chemical Substances	Antigens
Language	English
Publishing date	2023-04-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20220595
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Article ; Online: IRF5 guides monocytes toward an inflammatory CD11c

Corbin, Alastair L / Gomez-Vazquez, Maria / Berthold, Dorothée L / Attar, Moustafa / Arnold, Isabelle C / Powrie, Fiona M / Sansom, Stephen N / Udalova, Irina A

Science immunology

2020 Volume 5, Issue 47

Abstract: Mononuclear phagocytes (MNPs) are vital for maintaining intestinal homeostasis but, in response to acute microbial stimulation, can also trigger immunopathology, accelerating recruitment of ... ...

Abstract	Mononuclear phagocytes (MNPs) are vital for maintaining intestinal homeostasis but, in response to acute microbial stimulation, can also trigger immunopathology, accelerating recruitment of Ly6C
MeSH term(s)	Animals ; CD11 Antigens/immunology ; Helicobacter hepaticus/immunology ; Inflammation/immunology ; Inflammation/pathology ; Interferon Regulatory Factors/deficiency ; Interferon Regulatory Factors/immunology ; Macrophages/immunology ; Macrophages/pathology ; Mice ; Mice, Knockout ; Monocytes/immunology ; Monocytes/pathology ; Phenotype
Chemical Substances	CD11 Antigens ; Interferon Regulatory Factors ; Irf5 protein, mouse ; Itgax protein, mouse
Language	English
Publishing date	2020-05-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.aax6085
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Article ; Online: Defactinib inhibits PYK2 phosphorylation of IRF5 and reduces intestinal inflammation.

Ryzhakov, Grigory / Almuttaqi, Hannah / Corbin, Alastair L / Berthold, Dorothée L / Khoyratty, Tariq / Eames, Hayley L / Bullers, Samuel / Pearson, Claire / Ai, Zhichao / Zec, Kristina / Bonham, Sarah / Fischer, Roman / Jostins-Dean, Luke / Travis, Simon P L / Kessler, Benedikt M / Udalova, Irina A

Nature communications

2021 Volume 12, Issue 1, Page(s) 6702

Abstract: Interferon regulating factor 5 (IRF5) is a multifunctional regulator of immune responses, and has a key pathogenic function in gut inflammation, but how IRF5 is modulated is still unclear. Having performed a kinase inhibitor library screening in ... ...

Abstract	Interferon regulating factor 5 (IRF5) is a multifunctional regulator of immune responses, and has a key pathogenic function in gut inflammation, but how IRF5 is modulated is still unclear. Having performed a kinase inhibitor library screening in macrophages, here we identify protein-tyrosine kinase 2-beta (PTK2B/PYK2) as a putative IRF5 kinase. PYK2-deficient macrophages display impaired endogenous IRF5 activation, leading to reduction of inflammatory gene expression. Meanwhile, a PYK2 inhibitor, defactinib, has a similar effect on IRF5 activation in vitro, and induces a transcriptomic signature in macrophages similar to that caused by IRF5 deficiency. Finally, defactinib reduces pro-inflammatory cytokines in human colon biopsies from patients with ulcerative colitis, as well as in a mouse colitis model. Our results thus implicate a function of PYK2 in regulating the inflammatory response in the gut via the IRF5 innate sensing pathway, thereby opening opportunities for related therapeutic interventions for inflammatory bowel diseases and other inflammatory conditions.
MeSH term(s)	Animals ; Benzamides/pharmacology ; Cells, Cultured ; Colitis/genetics ; Colitis/metabolism ; Colitis/prevention & control ; Cytokines/genetics ; Cytokines/metabolism ; Focal Adhesion Kinase 2/genetics ; Focal Adhesion Kinase 2/metabolism ; Gene Expression Profiling/methods ; HEK293 Cells ; Humans ; Inflammation/genetics ; Inflammation/metabolism ; Inflammation/prevention & control ; Interferon Regulatory Factors/genetics ; Interferon Regulatory Factors/metabolism ; Intestines/pathology ; Macrophages/drug effects ; Macrophages/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mutation ; Phosphorylation/drug effects ; Pyrazines/pharmacology ; RAW 264.7 Cells ; Sulfonamides/pharmacology
Chemical Substances	Benzamides ; Cytokines ; Interferon Regulatory Factors ; Irf5 protein, mouse ; Pyrazines ; Sulfonamides ; defactinib (53O87HA2QU) ; Focal Adhesion Kinase 2 (EC 2.7.10.2) ; Ptk2b protein, mouse (EC 2.7.10.2)
Language	English
Publishing date	2021-11-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-27038-5
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Article ; Online: Intestinal epithelial NAIP/NLRC4 restricts systemic dissemination of the adapted pathogen Salmonella Typhimurium due to site-specific bacterial PAMP expression.

Hausmann, Annika / Böck, Desirée / Geiser, Petra / Berthold, Dorothée L / Fattinger, Stefan A / Furter, Markus / Bouman, Judith A / Barthel-Scherrer, Manja / Lang, Crispin M / Bakkeren, Erik / Kolinko, Isabel / Diard, Médéric / Bumann, Dirk / Slack, Emma / Regoes, Roland R / Pilhofer, Martin / Sellin, Mikael E / Hardt, Wolf-Dietrich

Mucosal immunology

2020 Volume 13, Issue 3, Page(s) 530–544

Abstract: Inflammasomes can prevent systemic dissemination of enteropathogenic bacteria. As adapted pathogens including Salmonella Typhimurium (S. Tm) have evolved evasion strategies, it has remained unclear when and where inflammasomes restrict their ... ...

Abstract	Inflammasomes can prevent systemic dissemination of enteropathogenic bacteria. As adapted pathogens including Salmonella Typhimurium (S. Tm) have evolved evasion strategies, it has remained unclear when and where inflammasomes restrict their dissemination. Bacterial population dynamics establish that the NAIP/NLRC4 inflammasome specifically restricts S. Tm migration from the gut to draining lymph nodes. This is solely attributable to NAIP/NLRC4 within intestinal epithelial cells (IECs), while S. Tm evades restriction by phagocyte NAIP/NLRC4. NLRP3 and Caspase-11 also fail to restrict S. Tm mucosa traversal, migration to lymph nodes, and systemic pathogen growth. The ability of IECs (not phagocytes) to mount a NAIP/NLRC4 defense in vivo is explained by particularly high NAIP/NLRC4 expression in IECs and the necessity for epithelium-invading S. Tm to express the NAIP1-6 ligands-flagella and type-III-secretion-system-1. Imaging reveals both ligands to be promptly downregulated following IEC-traversal. These results highlight the importance of intestinal epithelial NAIP/NLRC4 in blocking bacterial dissemination in vivo, and explain why this constitutes a uniquely evasion-proof defense against the adapted enteropathogen S. Tm.
MeSH term(s)	Animals ; CARD Signaling Adaptor Proteins/metabolism ; Calcium-Binding Proteins/metabolism ; Caspases/metabolism ; Disease Models, Animal ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Intestinal Mucosa/immunology ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/microbiology ; Lymphoid Tissue/immunology ; Lymphoid Tissue/metabolism ; Mice ; Mice, Knockout ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Neuronal Apoptosis-Inhibitory Protein/metabolism ; Organ Specificity/immunology ; Pathogen-Associated Molecular Pattern Molecules ; Phagocytes/immunology ; Phagocytes/metabolism ; Salmonella Infections/immunology ; Salmonella Infections/metabolism ; Salmonella Infections/microbiology ; Salmonella typhimurium/genetics ; Salmonella typhimurium/immunology
Chemical Substances	CARD Signaling Adaptor Proteins ; Calcium-Binding Proteins ; NAIP protein, human ; NLR Family, Pyrin Domain-Containing 3 Protein ; NLRC4 protein, human ; NLRP3 protein, human ; Neuronal Apoptosis-Inhibitory Protein ; Pathogen-Associated Molecular Pattern Molecules ; Caspases (EC 3.4.22.-) ; caspase 11, human (EC 3.4.22.-)
Language	English
Publishing date	2020-01-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2411370-0
ISSN	1935-3456 ; 1933-0219
ISSN (online)	1935-3456
ISSN	1933-0219
DOI	10.1038/s41385-019-0247-0
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Article ; Online: Escherichia coli limits Salmonella Typhimurium infections after diet shifts and fat-mediated microbiota perturbation in mice.

Wotzka, Sandra Y / Kreuzer, Markus / Maier, Lisa / Arnoldini, Markus / Nguyen, Bidong D / Brachmann, Alexander O / Berthold, Dorothée L / Zünd, Mirjam / Hausmann, Annika / Bakkeren, Erik / Hoces, Daniel / Gül, Ersin / Beutler, Markus / Dolowschiak, Tamas / Zimmermann, Michael / Fuhrer, Tobias / Moor, Kathrin / Sauer, Uwe / Typas, Athanasios /

Piel, Jörn / Diard, Médéric / Macpherson, Andrew J / Stecher, Bärbel / Sunagawa, Shinichi / Slack, Emma / Hardt, Wolf-Dietrich

Nature microbiology

2019 Volume 4, Issue 12, Page(s) 2164–2174

Abstract: The microbiota confers colonization resistance, which blocks Salmonella gut ... ...

Abstract	The microbiota confers colonization resistance, which blocks Salmonella gut colonization
MeSH term(s)	Animal Feed ; Animals ; Bile Acids and Salts/administration & dosage ; Dietary Fats/administration & dosage ; Escherichia coli/physiology ; Female ; Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Male ; Mice ; Mice, Inbred C57BL ; Microbial Interactions ; Oleic Acids/administration & dosage ; Salmonella typhimurium/physiology
Chemical Substances	Bile Acids and Salts ; Dietary Fats ; Oleic Acids
Language	English
Publishing date	2019-10-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/s41564-019-0568-5
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Article ; Online: Intercrypt sentinel macrophages tune antibacterial NF-κB responses in gut epithelial cells via TNF.

Hausmann, Annika / Felmy, Boas / Kunz, Leo / Kroon, Sanne / Berthold, Dorothée Lisa / Ganz, Giverny / Sandu, Ioana / Nakamura, Toshihiro / Zangger, Nathan Sébastien / Zhang, Yang / Dolowschiak, Tamas / Fattinger, Stefan Alexander / Furter, Markus / Müller-Hauser, Anna Angelika / Barthel, Manja / Vlantis, Katerina / Wachsmuth, Laurens / Kisielow, Jan / Tortola, Luigi /

Heide, Danijela / Heikenwälder, Mathias / Oxenius, Annette / Kopf, Manfred / Schroeder, Timm / Pasparakis, Manolis / Sellin, Mikael Erik / Hardt, Wolf-Dietrich

The Journal of experimental medicine

2021 Volume 218, Issue 11

Abstract: Intestinal epithelial cell (IEC) NF-κB signaling regulates the balance between mucosal homeostasis and inflammation. It is not fully understood which signals tune this balance and how bacterial exposure elicits the process. Pure LPS induces epithelial NF- ...

Abstract	Intestinal epithelial cell (IEC) NF-κB signaling regulates the balance between mucosal homeostasis and inflammation. It is not fully understood which signals tune this balance and how bacterial exposure elicits the process. Pure LPS induces epithelial NF-κB activation in vivo. However, we found that in mice, IECs do not respond directly to LPS. Instead, tissue-resident lamina propria intercrypt macrophages sense LPS via TLR4 and rapidly secrete TNF to elicit epithelial NF-κB signaling in their immediate neighborhood. This response pattern is relevant also during oral enteropathogen infection. The macrophage-TNF-IEC axis avoids responses to luminal microbiota LPS but enables crypt- or tissue-scale epithelial NF-κB responses in proportion to the microbial threat. Thereby, intercrypt macrophages fulfill important sentinel functions as first responders to Gram-negative microbes breaching the epithelial barrier. The tunability of this crypt response allows the induction of defense mechanisms at an appropriate scale according to the localization and intensity of microbial triggers.
MeSH term(s)	Animals ; Anti-Bacterial Agents/metabolism ; Epithelial Cells/metabolism ; Gene Expression Regulation/physiology ; Inflammation/metabolism ; Intestinal Mucosa/metabolism ; Intestines/metabolism ; Macrophages/drug effects ; Mice ; Mice, Inbred C57BL ; NF-kappa B/metabolism ; Signal Transduction/physiology ; Tumor Necrosis Factors/metabolism
Chemical Substances	Anti-Bacterial Agents ; NF-kappa B ; Tumor Necrosis Factors
Language	English
Publishing date	2021-09-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20210862
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Article ; Online: Development of a Novel CD4

Fernandez-Ruiz, Daniel / Lau, Lei Shong / Ghazanfari, Nazanin / Jones, Claerwen M / Ng, Wei Yi / Davey, Gayle M / Berthold, Dorothee / Holz, Lauren / Kato, Yu / Enders, Matthias H / Bayarsaikhan, Ganchimeg / Hendriks, Sanne H / Lansink, Lianne I M / Engel, Jessica A / Soon, Megan S F / James, Kylie R / Cozijnsen, Anton / Mollard, Vanessa / Uboldi, Alessandro D /

Tonkin, Christopher J / de Koning-Ward, Tania F / Gilson, Paul R / Kaisho, Tsuneyasu / Haque, Ashraful / Crabb, Brendan S / Carbone, Francis R / McFadden, Geoffrey I / Heath, William R

Journal of immunology (Baltimore, Md. : 1950)

2017

Abstract: We describe an MHC class II (I- ... ...

Abstract	We describe an MHC class II (I-A
Language	English
Publishing date	2017-10-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1700186
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Article ; Online: RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis.

Lichtinger, Monika / Ingram, Richard / Hannah, Rebecca / Müller, Dorothee / Clarke, Deborah / Assi, Salam A / Lie-A-Ling, Michael / Noailles, Laura / Vijayabaskar, M S / Wu, Mengchu / Tenen, Daniel G / Westhead, David R / Kouskoff, Valerie / Lacaud, Georges / Göttgens, Berthold / Bonifer, Constanze

The EMBO journal

2012 Volume 31, Issue 22, Page(s) 4318–4333

Abstract: Cell fate decisions during haematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. To gain insight into how these transcription factors regulate the activation of haematopoietic genes ...

Abstract	Cell fate decisions during haematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. To gain insight into how these transcription factors regulate the activation of haematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from haemogenic endothelium (HE) to haematopoietic progenitors. Using a Runx1-/- embryonic stem cell differentiation model expressing an inducible Runx1 gene, we show that in the absence of RUNX1, haematopoietic genes bind SCL/TAL1, FLI1 and C/EBPβ and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous de novo sites, initiating a local increase in histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of haematopoietic fate controlled by Runx1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing HE program but instead entails global reorganization of lineage-specific transcription factor assemblies.
MeSH term(s)	Acetylation ; Animals ; Base Sequence ; Cell Line ; Core Binding Factor Alpha 2 Subunit/genetics ; Core Binding Factor Alpha 2 Subunit/physiology ; Embryonic Stem Cells/physiology ; Epigenesis, Genetic/genetics ; Epigenesis, Genetic/physiology ; Hematopoiesis/genetics ; Hematopoiesis/physiology ; Histones/metabolism ; Mice ; Molecular Sequence Data ; Protein Binding ; Transcription Factors/physiology
Chemical Substances	Core Binding Factor Alpha 2 Subunit ; Histones ; Runx1 protein, mouse ; Transcription Factors
Language	English
Publishing date	2012-10-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	586044-1
ISSN	1460-2075 ; 0261-4189
ISSN (online)	1460-2075
ISSN	0261-4189
DOI	10.1038/emboj.2012.275
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