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Article ; Online: Epithelial-neuronal-immune cell interactions: Implications for immunity, inflammation, and tissue homeostasis at mucosal sites.

Emanuel, Elizabeth / Arifuzzaman, Mohammad / Artis, David

The Journal of allergy and clinical immunology

2024

Abstract: The epithelial lining of the respiratory tract and intestine provides a critical physical barrier to protect host tissues against environmental insults, including dietary antigens, allergens, chemicals, and microorganisms. In addition, specialized ... ...

Abstract	The epithelial lining of the respiratory tract and intestine provides a critical physical barrier to protect host tissues against environmental insults, including dietary antigens, allergens, chemicals, and microorganisms. In addition, specialized epithelial cells communicate directly with hematopoietic and neuronal cells. These epithelial-immune and epithelial-neuronal interactions control host immune responses and have important implications for inflammatory conditions associated with defects in the epithelial barrier, including asthma, allergy, and inflammatory bowel diseases. In this review, we discuss emerging research that identifies the mechanisms and impact of epithelial-immune and epithelial-neuronal cross talk in regulating immunity, inflammation, and tissue homeostasis at mucosal barrier surfaces. Understanding the regulation and impact of these pathways could provide new therapeutic targets for inflammatory diseases at mucosal sites.
Language	English
Publishing date	2024-02-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2024.02.004
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Article ; Online: Nutritional regulation of microbiota-derived metabolites: Implications for immunity and inflammation.

Arifuzzaman, Mohammad / Collins, Nicholas / Guo, Chun-Jun / Artis, David

Immunity

2024 Volume 57, Issue 1, Page(s) 14–27

Abstract: Nutrition profoundly shapes immunity and inflammation across the lifespan of mammals, from pre- and post-natal periods to later life. Emerging insights into diet-microbiota interactions indicate that nutrition has a dominant influence on the composition- ... ...

Abstract	Nutrition profoundly shapes immunity and inflammation across the lifespan of mammals, from pre- and post-natal periods to later life. Emerging insights into diet-microbiota interactions indicate that nutrition has a dominant influence on the composition-and metabolic output-of the intestinal microbiota, which in turn has major consequences for host immunity and inflammation. Here, we discuss recent findings that support the concept that dietary effects on microbiota-derived metabolites potently alter immune responses in health and disease. We discuss how specific dietary components and metabolites can be either pro-inflammatory or anti-inflammatory in a context- and tissue-dependent manner during infection, chronic inflammation, and cancer. Together, these studies emphasize the influence of diet-microbiota crosstalk on immune regulation that will have a significant impact on precision nutrition approaches and therapeutic interventions for managing inflammation, infection, and cancer immunotherapy.
MeSH term(s)	Animals ; Inflammation ; Microbiota ; Gastrointestinal Microbiome ; Cross Reactions ; Neoplasms/therapy ; Mammals
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2023.12.009
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Zs.A 4227: 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: Dietary fiber is a critical determinant of pathologic ILC2 responses and intestinal inflammation.

Arifuzzaman, Mohammad / Won, Tae Hyung / Yano, Hiroshi / Uddin, Jazib / Emanuel, Elizabeth R / Hu, Elin / Zhang, Wen / Li, Ting-Ting / Jin, Wen-Bing / Grier, Alex / Kashyap, Sanchita / Guo, Chun-Jun / Schroeder, Frank C / Artis, David

The Journal of experimental medicine

2024 Volume 221, Issue 5

Abstract: Innate lymphoid cells (ILCs) can promote host defense, chronic inflammation, or tissue protection and are regulated by cytokines and neuropeptides. However, their regulation by diet and microbiota-derived signals remains unclear. We show that an inulin ... ...

Abstract	Innate lymphoid cells (ILCs) can promote host defense, chronic inflammation, or tissue protection and are regulated by cytokines and neuropeptides. However, their regulation by diet and microbiota-derived signals remains unclear. We show that an inulin fiber diet promotes Tph1-expressing inflammatory ILC2s (ILC2INFLAM) in the colon, which produce IL-5 but not tissue-protective amphiregulin (AREG), resulting in the accumulation of eosinophils. This exacerbates inflammation in a murine model of intestinal damage and inflammation in an ILC2- and eosinophil-dependent manner. Mechanistically, the inulin fiber diet elevated microbiota-derived bile acids, including cholic acid (CA) that induced expression of ILC2-activating IL-33. In IBD patients, bile acids, their receptor farnesoid X receptor (FXR), IL-33, and eosinophils were all upregulated compared with controls, implicating this diet-microbiota-ILC2 axis in human IBD pathogenesis. Together, these data reveal that dietary fiber-induced changes in microbial metabolites operate as a rheostat that governs protective versus pathologic ILC2 responses with relevance to precision nutrition for inflammatory diseases.
MeSH term(s)	Humans ; Animals ; Mice ; Immunity, Innate ; Interleukin-33 ; Inulin ; Lymphocytes ; Dietary Fiber ; Bile Acids and Salts ; Inflammation ; Inflammatory Bowel Diseases
Chemical Substances	Interleukin-33 ; Inulin (9005-80-5) ; Dietary Fiber ; Bile Acids and Salts
Language	English
Publishing date	2024-03-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20232148
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Ua VI Zs.107: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Microbiota metabolism of intestinal amino acids impacts host nutrient homeostasis and physiology.

Li, Ting-Ting / Chen, Xi / Huo, Da / Arifuzzaman, Mohammad / Qiao, Shanshan / Jin, Wen-Bing / Shi, Huiqing / Li, Xin V / Iliev, Iliyan D / Artis, David / Guo, Chun-Jun

Cell host & microbe

2024

Abstract: The intestine and liver are thought to metabolize dietary nutrients and regulate host nutrient homeostasis. Here, we find that the gut microbiota also reshapes the host amino acid (aa) landscape via efficiently metabolizing intestinal aa. To identify the ...

Abstract	The intestine and liver are thought to metabolize dietary nutrients and regulate host nutrient homeostasis. Here, we find that the gut microbiota also reshapes the host amino acid (aa) landscape via efficiently metabolizing intestinal aa. To identify the responsible microbes/genes, we developed a metabolomics-based assay to screen 104 commensals and identified candidates that efficiently utilize aa. Using genetics, we identified multiple responsible metabolic genes in phylogenetically diverse microbes. By colonizing germ-free mice with the wild-type strain and their isogenic mutant deficient in individual aa-metabolizing genes, we found that these genes regulate the availability of gut and circulatory aa. Notably, microbiota genes for branched-chain amino acids (BCAAs) and tryptophan metabolism indirectly affect host glucose homeostasis via peripheral serotonin. Collectively, at single-gene level, this work characterizes a microbiota-encoded metabolic activity that affects host nutrient homeostasis and provides a roadmap to interrogate microbiota-dependent activity to improve human health.
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2024.04.004
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Zs.A 6578: Show issues

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Article ; Online: Contrast agents for x-ray luminescence computed tomography.

Lun, Michael C / Ranasinghe, Meenakshi / Arifuzzaman, Mohammad / Fang, Yile / Guo, Yiping / Anker, Jeffrey N / Li, Changqing

Applied optics

2021 Volume 60, Issue 23, Page(s) 6769–6775

Abstract: Imaging probes are an important consideration for any type of contrast agent-based imaging method. X-ray luminescence imaging (XLI) and x-ray luminescence computed tomography (XLCT) are both contrast agent-based imaging methods that employ x-ray ... ...

Abstract	Imaging probes are an important consideration for any type of contrast agent-based imaging method. X-ray luminescence imaging (XLI) and x-ray luminescence computed tomography (XLCT) are both contrast agent-based imaging methods that employ x-ray excitable scintillating imaging probes that emit light to be measured for optical imaging. In this work, we compared the performance of several select imaging probes, both commercial and self-synthesized, for application in XLI/XLCT imaging. Commercially available cadmium telluride quantum dots (CdTe QDs) and europium-doped gadolinium oxysulfide (GOS:Eu) microphosphor as well as synthesized
MeSH term(s)	Cadmium Compounds/chemistry ; Contrast Media/chemistry ; Erbium/chemistry ; Europium/chemistry ; Fluorides/chemistry ; Gadolinium/chemistry ; Image Processing, Computer-Assisted/methods ; Luminescence ; Optical Imaging/methods ; Phantoms, Imaging ; Quantum Dots ; Tellurium/chemistry ; Tomography, X-Ray Computed/methods
Chemical Substances	Cadmium Compounds ; Contrast Media ; NaGdF4 ; gadolinium sulfoxylate (12339-07-0) ; Europium (444W947O8O) ; Erbium (77B218D3YE) ; Gadolinium (AU0V1LM3JT) ; Tellurium (NQA0O090ZJ) ; Fluorides (Q80VPU408O) ; cadmium telluride (STG188WO13)
Language	English
Publishing date	2021-09-23
Publishing country	United States
Document type	Journal Article
ISSN	1539-4522
ISSN (online)	1539-4522
DOI	10.1364/AO.431080
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Article ; Online: The ChAT-acetylcholine pathway promotes group 2 innate lymphoid cell responses and anti-helminth immunity.

Chu, Coco / Parkhurst, Christopher N / Zhang, Wen / Zhou, Lei / Yano, Hiroshi / Arifuzzaman, Mohammad / Artis, David

Science immunology

2021 Volume 6, Issue 57

Abstract: Group 2 innate lymphoid cells (ILC2s) reside in multiple tissues, including lymphoid organs and barrier surfaces, and secrete type 2 cytokines including interleukin-5 (IL-5), IL-9, and IL-13. These cells participate in multiple physiological processes ... ...

Abstract	Group 2 innate lymphoid cells (ILC2s) reside in multiple tissues, including lymphoid organs and barrier surfaces, and secrete type 2 cytokines including interleukin-5 (IL-5), IL-9, and IL-13. These cells participate in multiple physiological processes including allergic inflammation, tissue repair, metabolic homeostasis, and host defense against helminth infections. Recent studies indicate that neurotransmitters and neuropeptides can play an important role in regulating ILC2 responses; however, the mechanisms that underlie these processes in vivo remain incompletely defined. Here, we identify that activated ILC2s up-regulate choline acetyltransferase (ChAT)-the enzyme responsible for the biosynthesis of acetylcholine (ACh)-after infection with the helminth parasite
MeSH term(s)	Acetylcholine/metabolism ; Animals ; Biomarkers ; Choline O-Acetyltransferase/genetics ; Choline O-Acetyltransferase/metabolism ; Cytokines/metabolism ; Disease Models, Animal ; Eosinophils/immunology ; Eosinophils/metabolism ; Gene Expression ; Helminthiasis/immunology ; Helminthiasis/metabolism ; Helminthiasis/parasitology ; Helminths/immunology ; Host-Parasite Interactions/immunology ; Humans ; Immunity, Innate ; Immunophenotyping ; Lymphocyte Subsets/immunology ; Lymphocyte Subsets/metabolism ; Mice
Chemical Substances	Biomarkers ; Cytokines ; Choline O-Acetyltransferase (EC 2.3.1.6) ; Acetylcholine (N9YNS0M02X)
Language	English
Publishing date	2021-03-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.abe3218
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Article ; Online: Focused x-ray luminescence imaging system for small animals based on a rotary gantry.

Lun, Michael C / Cong, Wenxiang / Arifuzzaman, Mohammad / Ranasinghe, Meenakshi / Bhattacharya, Sriparna / Anker, Jeffrey N / Wang, Ge / Li, Changqing

Journal of biomedical optics

2021 Volume 26, Issue 3

Abstract: Significance: The ability to detect and localize specific molecules through tissue is important for elucidating the molecular basis of disease and treatment. Unfortunately, most current molecular imaging tools in tissue either lack high spatial ... ...

Abstract	Significance: The ability to detect and localize specific molecules through tissue is important for elucidating the molecular basis of disease and treatment. Unfortunately, most current molecular imaging tools in tissue either lack high spatial resolution (e.g., diffuse optical fluorescence tomography or positron emission tomography) or lack molecular sensitivity (e.g., micro-computed tomography, μCT). X-ray luminescence imaging emerged about 10 years ago to address this issue by combining the molecular sensitivity of optical probes with the high spatial resolution of x-ray imaging through tissue. In particular, x-ray luminescence computed tomography (XLCT) has been demonstrated as a powerful technique for the high-resolution imaging of deeply embedded contrast agents in three dimensions (3D) for small-animal imaging. Aim: To facilitate the translation of XLCT for small-animal imaging, we have designed and built a small-animal dedicated focused x-ray luminescence tomography (FXLT) scanner with a μCT scanner, synthesized bright and biocompatible nanophosphors as contrast agents, and have developed a deep-learning-based reconstruction algorithm. Approach: The proposed FXLT imaging system was designed using computer-aided design software and built according to specifications. NaGdF4 nanophosphors doped with europium or terbium were synthesized with a silica shell for increased biocompatibility and functionalized with biotin. A deep-learning-based XLCT image reconstruction was also developed based on the residual neural network as a data synthesis method of projection views from few-view data to enhance the reconstructed image quality. Results: We have built the FXLT scanner for small-animal imaging based on a rotational gantry. With all major imaging components mounted, the motor controlling the gantry can be used to rotate the system with a high accuracy. The synthesized nanophosphors displayed distinct x-ray luminescence emission, which enables multi-color imaging, and has successfully been bound to streptavidin-coated substrates. Lastly, numerical simulations using the proposed deep-learning-based reconstruction algorithm has demonstrated a clear enhancement in the reconstructed image quality. Conclusions: The designed FXLT scanner, synthesized nanophosphors, and deep-learning-based reconstruction algorithm show great potential for the high-resolution molecular imaging of small animals.
MeSH term(s)	Algorithms ; Animals ; Fluorides ; Gadolinium ; Image Processing, Computer-Assisted ; Luminescence ; Phantoms, Imaging ; X-Ray Microtomography ; X-Rays
Chemical Substances	NaGdF4 ; Gadolinium (AU0V1LM3JT) ; Fluorides (Q80VPU408O)
Language	English
Publishing date	2021-03-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1309154-2
ISSN	1560-2281 ; 1083-3668
ISSN (online)	1560-2281
ISSN	1083-3668
DOI	10.1117/1.JBO.26.3.036004
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Zs.A 4699: Show issues

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Article ; Online: Genetic manipulation of gut microbes enables single-gene interrogation in a complex microbiome.

Jin, Wen-Bing / Li, Ting-Ting / Huo, Da / Qu, Sophia / Li, Xin V / Arifuzzaman, Mohammad / Lima, Svetlana F / Shi, Hui-Qing / Wang, Aolin / Putzel, Gregory G / Longman, Randy S / Artis, David / Guo, Chun-Jun

Cell

2022 Volume 185, Issue 3, Page(s) 547–562.e22

Abstract: Hundreds of microbiota genes are associated with host biology/disease. Unraveling the causal contribution of a microbiota gene to host biology remains difficult because many are encoded by nonmodel gut commensals and not genetically targetable. A general ...

Abstract	Hundreds of microbiota genes are associated with host biology/disease. Unraveling the causal contribution of a microbiota gene to host biology remains difficult because many are encoded by nonmodel gut commensals and not genetically targetable. A general approach to identify their gene transfer methodology and build their gene manipulation tools would enable mechanistic dissections of their impact on host physiology. We developed a pipeline that identifies the gene transfer methods for multiple nonmodel microbes spanning five phyla, and we demonstrated the utility of their genetic tools by modulating microbiome-derived short-chain fatty acids and bile acids in vitro and in the host. In a proof-of-principle study, by deleting a commensal gene for bile acid synthesis in a complex microbiome, we discovered an intriguing role of this gene in regulating colon inflammation. This technology will enable genetically engineering the nonmodel gut microbiome and facilitate mechanistic dissection of microbiota-host interactions.
MeSH term(s)	Animals ; Bile Acids and Salts/metabolism ; CRISPR-Cas Systems/genetics ; Clostridium/genetics ; Colitis/chemically induced ; Colitis/microbiology ; Colitis/pathology ; Dextran Sulfate ; Drug Resistance, Microbial/genetics ; Female ; Gastrointestinal Microbiome/genetics ; Gene Expression Regulation, Bacterial ; Gene Transfer Techniques ; Genes, Bacterial ; Germ-Free Life ; Inflammation/pathology ; Intestines/pathology ; Male ; Metabolome/genetics ; Metagenomics ; Mice, Inbred C57BL ; Mice, Knockout ; Mutagenesis, Insertional/genetics ; Mutation/genetics ; RNA, Ribosomal, 16S/genetics ; Transcription, Genetic ; Mice
Chemical Substances	Bile Acids and Salts ; RNA, Ribosomal, 16S ; Dextran Sulfate (9042-14-2)
Language	English
Publishing date	2022-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2021.12.035
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Zs.A 1167: 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: Genetic manipulation of gut microbes enables single-gene interrogation in a complex microbiome

Jin, Wen-Bing / Li, Ting-Ting / Huo, Da / Qu, Sophia / Li, Xin V. / Arifuzzaman, Mohammad / Lima, Svetlana F. / Shi, Hui-Qing / Wang, Aolin / Putzel, Gregory G. / Longman, Randy S. / Artis, David / Guo, Chun-Jun

Cell. 2022 Feb. 03, v. 185, no. 3

2022

Abstract	Hundreds of microbiota genes are associated with host biology/disease. Unraveling the causal contribution of a microbiota gene to host biology remains difficult because many are encoded by nonmodel gut commensals and not genetically targetable. A general approach to identify their gene transfer methodology and build their gene manipulation tools would enable mechanistic dissections of their impact on host physiology. We developed a pipeline that identifies the gene transfer methods for multiple nonmodel microbes spanning five phyla, and we demonstrated the utility of their genetic tools by modulating microbiome-derived short-chain fatty acids and bile acids in vitro and in the host. In a proof-of-principle study, by deleting a commensal gene for bile acid synthesis in a complex microbiome, we discovered an intriguing role of this gene in regulating colon inflammation. This technology will enable genetically engineering the nonmodel gut microbiome and facilitate mechanistic dissection of microbiota-host interactions.
Keywords	bile ; bile acids ; colon ; dissection ; gene transfer ; genes ; genetic engineering ; inflammation ; intestinal microorganisms ; microbiome ; physiology
Language	English
Dates of publication	2022-0203
Size	p. 547-562.e22.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2021.12.035
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Transcutaneous Vaccination with Conjugate Typhoid Vaccine Vi-DT Induces Systemic, Mucosal, and Memory Anti-Polysaccharide Responses.

Bhuiyan, Md Saruar / Kalsy, Anuj / Arifuzzaman, Mohammad / Charles, Richelle C / Harris, Jason B / Calderwood, Stephen B / Qadri, Firdausi / Ryan, Edward T

The American journal of tropical medicine and hygiene

2020 Volume 103, Issue 3, Page(s) 1032–1038

Abstract: Transcutaneous vaccination can induce both mucosal and systemic immune responses. However, there are few data on anti-polysaccharide responses following transcutaneous vaccination of polysaccharides, despite the role that anti-polysaccharide responses ... ...

Abstract	Transcutaneous vaccination can induce both mucosal and systemic immune responses. However, there are few data on anti-polysaccharide responses following transcutaneous vaccination of polysaccharides, despite the role that anti-polysaccharide responses play in protecting against intestinal mucosal and respiratory pathogens. Whether transcutaneous vaccination with a conjugate polysaccharide vaccine would be able to induce memory responses is also unknown. To address this, we transcutaneously vaccinated mice with virulence antigen (Vi) polysaccharide of
MeSH term(s)	Administration, Cutaneous ; Animals ; Antibodies, Bacterial/blood ; Disease Models, Animal ; Female ; Humans ; Immunity, Humoral/drug effects ; Immunity, Mucosal/drug effects ; Immunization Schedule ; Immunoglobulin A/blood ; Immunoglobulin G/blood ; Immunologic Memory/drug effects ; Mice ; Polysaccharides, Bacterial/chemistry ; Polysaccharides, Bacterial/immunology ; Salmonella typhi/drug effects ; Salmonella typhi/immunology ; Salmonella typhi/pathogenicity ; Typhoid Fever/immunology ; Typhoid Fever/microbiology ; Typhoid Fever/prevention & control ; Typhoid-Paratyphoid Vaccines/administration & dosage ; Typhoid-Paratyphoid Vaccines/biosynthesis ; Vaccination/methods ; Vaccines, Conjugate
Chemical Substances	Antibodies, Bacterial ; Immunoglobulin A ; Immunoglobulin G ; Polysaccharides, Bacterial ; Typhoid-Paratyphoid Vaccines ; Vaccines, Conjugate
Language	English
Publishing date	2020-07-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2942-7
ISSN	1476-1645 ; 0002-9637
ISSN (online)	1476-1645
ISSN	0002-9637
DOI	10.4269/ajtmh.19-0798
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