scholarly journals Organoids to Dissect Gastrointestinal Virus–Host Interactions: What Have We Learned?

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 999
Author(s):  
Sue E. Crawford ◽  
Sasirekha Ramani ◽  
Sarah E. Blutt ◽  
Mary K. Estes
Keyword(s):  
Cell Types ◽  
Human Infection ◽  
Viral Pathogens ◽  
Host Interactions ◽  
Complex Interactions ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Human Intestinal Epithelium ◽  
Human Viruses ◽  
Human Infections

Historically, knowledge of human host–enteric pathogen interactions has been elucidated from studies using cancer cells, animal models, clinical data, and occasionally, controlled human infection models. Although much has been learned from these studies, an understanding of the complex interactions between human viruses and the human intestinal epithelium was initially limited by the lack of nontransformed culture systems, which recapitulate the relevant heterogenous cell types that comprise the intestinal villus epithelium. New investigations using multicellular, physiologically active, organotypic cultures produced from intestinal stem cells isolated from biopsies or surgical specimens provide an exciting new avenue for understanding human specific pathogens and revealing previously unknown host–microbe interactions that affect replication and outcomes of human infections. Here, we summarize recent biologic discoveries using human intestinal organoids and human enteric viral pathogens.

scholarly journals Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
David R Hill ◽  
Sha Huang ◽  
Melinda S Nagy ◽  
Veda K Yadagiri ◽  
Courtney Fields ◽  
...  
Keyword(s):  
Bacterial Colonization ◽  
Microbial Colonization ◽  
Human Pluripotent Stem Cell ◽  
Complex Environment ◽  
Human Gastrointestinal Tract ◽  
Oral Nutrition ◽  
Host Interactions ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Human Intestinal Epithelium

The human gastrointestinal tract is immature at birth, yet must adapt to dramatic changes such as oral nutrition and microbial colonization. The confluence of these factors can lead to severe inflammatory disease in premature infants; however, investigating complex environment-host interactions is difficult due to limited access to immature human tissue. Here, we demonstrate that the epithelium of human pluripotent stem-cell-derived human intestinal organoids is globally similar to the immature human epithelium and we utilize HIOs to investigate complex host-microbe interactions in this naive epithelium. Our findings demonstrate that the immature epithelium is intrinsically capable of establishing a stable host-microbe symbiosis. Microbial colonization leads to complex contact and hypoxia driven responses resulting in increased antimicrobial peptide production, maturation of the mucus layer, and improved barrier function. These studies lay the groundwork for an improved mechanistic understanding of how colonization influences development of the immature human intestine.

scholarly journals Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium

2017 ◽  
Author(s):  
David R. Hill ◽  
Sha Huang ◽  
Melinda S. Nagy ◽  
Veda K. Yadagiri ◽  
Courtney Fields ◽  
...  
Keyword(s):  
Bacterial Colonization ◽  
Microbial Colonization ◽  
Human Pluripotent Stem Cell ◽  
Complex Environment ◽  
Human Gastrointestinal Tract ◽  
Oral Nutrition ◽  
Host Interactions ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Human Intestinal Epithelium

AbstractThe human gastrointestinal tract is immature at birth, yet must adapt to dramatic changes such as oral nutrition and microbial colonization. The confluence of these factors can lead to severe inflammatory disease in premature infants; however, investigating complex environment-host interactions is diZcult due to limited access to immature human tissue. Here, we demonstrate that the epithelium of human pluripotent stem cell-derived human intestinal organoids is globally similar to the immature human epithelium and we utilize HIOs to investigate complex host-microbe interactions in this naïve epithelium. Our findings demonstrate that the immature epithelium is intrinsically capable of establishing a stable host-microbe symbiosis. Microbial colonization leads to complex contact and hypoxia driven responses resulting in increased antimicrobial peptide production, maturation of the mucus layer, and improved barrier function. These studies lay the groundwork for an improved mechanistic understanding of how colonization influences development of the immature human intestine.

scholarly journals A Cell Atlas of Microbe-Responsive Processes in the Zebrafish Intestine

2020 ◽  
Author(s):  
Reegan J. Willms ◽  
Jennifer C. Hocking ◽  
Edan Foley
Keyword(s):  
Transcriptional Activity ◽  
Cell Types ◽  
Cellular Heterogeneity ◽  
Host Responses ◽  
Cellular Specificity ◽  
Direct Growth ◽  
A Cell ◽  
Microbe Interactions ◽  
Regulatory Effects ◽  
Host Microbe Interactions

ABSTRACTGut microbial products direct growth, differentiation and development in the animal host. Disruptions to host-microbe interactions have profound health consequences, that include onset of chronic inflammatory illnesses. However, we lack system-wide understanding of cell-specific responses to the microbiome. We profiled transcriptional activity in individual cells from the intestine, and associated tissue, of zebrafish larvae that we raised in the presence, or absence, of a microbiome. We uncovered extensive cellular heterogeneity in the conventional zebrafish intestinal epithelium, including previously undescribed cell types with known mammalian homologs. By comparing conventional to germ-free profiles, we mapped microbial impacts on transcriptional activity in each cell population. We revealed intricate degrees of cellular specificity in host responses to the microbiome, that included regulatory effects on patterning, metabolic and immune activity. For example, we showed that removal of microbes hindered transduction of vascular endothelial growth factor-dependent signals in the developing vasculature, resulting in impaired intestinal vascularization. Our work provides a high-resolution atlas of intestinal cellular composition in the developing fish gut and details the effects of the microbiome on each cell type.

scholarly journals Mucosal microbial parasites/symbionts in health and disease: an integrative overview

Parasitology ◽  
2019 ◽  
Vol 146 (9) ◽  
pp. 1109-1115 ◽  
Author(s):  
Robert P. Hirt
Keyword(s):  
Host Interactions ◽  
Detection Techniques ◽  
Symbiotic Relationships ◽  
Life Styles ◽  
Mucosal Surfaces ◽  
Microbe Interactions ◽  
Health And Disease ◽  
Host Microbe Interactions ◽  
Species Being

AbstractMicrobial parasites adapted to thrive at mammalian mucosal surfaces have evolved multiple times from phylogenetically distant lineages into various extracellular and intracellular life styles. Their symbiotic relationships can range from commensalism to parasitism and more recently some host–parasites interactions are thought to have evolved into mutualistic associations too. It is increasingly appreciated that this diversity of symbiotic outcomes is the product of a complex network of parasites–microbiota–host interactions. Refinement and broader use of DNA based detection techniques are providing increasing evidence of how common some mucosal microbial parasites are and their host range, with some species being able to swap hosts, including from farm and pet animals to humans. A selection of examples will illustrate the zoonotic potential for a number of microbial parasites and how some species can be either disruptive or beneficial nodes in the complex networks of host–microbe interactions disrupting or maintaining mucosal homoeostasis. It will be argued that mucosal microbial parasitic diversity will represent an important resource to help us dissect through comparative studies the role of host–microbe interactions in both human health and disease.

scholarly journals Glycans in Virus-Host Interactions: A Structural Perspective

2021 ◽  
Vol 8 ◽  
Author(s):  
Nathaniel L. Miller ◽  
Thomas Clark ◽  
Rahul Raman ◽  
Ram Sasisekharan
Keyword(s):  
Immune System ◽  
Host Cells ◽  
Host Immune System ◽  
Host Interactions ◽  
Viral Glycoproteins ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Anti Hiv ◽  
Structural Perspective

Many interactions between microbes and their hosts are driven or influenced by glycans, whose heterogeneous and difficult to characterize structures have led to an underappreciation of their role in these interactions compared to protein-based interactions. Glycans decorate microbe glycoproteins to enhance attachment and fusion to host cells, provide stability, and evade the host immune system. Yet, the host immune system may also target these glycans as glycoepitopes. In this review, we provide a structural perspective on the role of glycans in host-microbe interactions, focusing primarily on viral glycoproteins and their interactions with host adaptive immunity. In particular, we discuss a class of topological glycoepitopes and their interactions with topological mAbs, using the anti-HIV mAb 2G12 as the archetypical example. We further offer our view that structure-based glycan targeting strategies are ready for application to viruses beyond HIV, and present our perspective on future development in this area.

Organoid Models for Infectious Disease

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Sarah E. Blutt ◽  
Mary K. Estes
Keyword(s):  
Infectious Diseases ◽  
Ex Vivo ◽  
Annual Review ◽  
Publication Date ◽  
Individual Health ◽  
Health Related ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Human Infections

Infectious diseases affect individual health and have widespread societal impacts. New ex vivo models are critical to understand pathogenesis, host response, and features necessary to develop preventive and therapeutic treatments. Pluripotent and tissue stem cell–derived organoids provide new tools for the study of human infections. Organoid models recapitulate many characteristics of in vivo disease and are providing new insights into human respiratory, gastrointestinal, and neuronal host–microbe interactions. Increasing culture complexity by adding the stroma, interorgan communication, and the microbiome will improve the use of organoids as models for infection. Organoid cultures provide a platform with the capability to improve human health related to infectious diseases. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Spatially Distinct Neutrophil Responses within the Inflammatory Lesions of Pneumonic Plague

mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
Nikolas M. Stasulli ◽  
Kara R. Eichelberger ◽  
Paul A. Price ◽  
Roger D. Pechous ◽  
Stephanie A. Montgomery ◽  
...  
Keyword(s):  
Yersinia Pestis ◽  
Cell Types ◽  
Lung Lesions ◽  
Pneumonic Plague ◽  
Content Type ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Neutrophil Survival

ABSTRACTDuring pneumonic plague, the bacteriumYersinia pestiselicits the development of inflammatory lung lesions that continue to expand throughout infection. This lesion development and persistence are poorly understood. Here, we examine spatially distinct regions of lung lesions using laser capture microdissection and transcriptome sequencing (RNA-seq) analysis to identify transcriptional differences between lesion microenvironments. We show that cellular pathways involved in leukocyte migration and apoptosis are downregulated in the center of lung lesions compared to the periphery. Probing for the bacterial factor(s) important for the alteration in neutrophil survival, we show bothin vitroandin vivothatY. pestisincreases neutrophil survival in a manner that is dependent on the type III secretion system effector YopM. This research explores the complexity of spatially distinct host-microbe interactions and emphasizes the importance of cell relevance in assays in order to fully understandY. pestisvirulence.IMPORTANCEYersinia pestisis a high-priority pathogen and continues to cause outbreaks worldwide. The ability ofY. pestisto be transmitted via respiratory droplets and its history of weaponization has led to its classification as a select agent most likely to be used as a biological weapon. Unrestricted bacterial growth during the initial preinflammatory phase primes patients to be infectious once disease symptoms begin in the proinflammatory phase, and the rapid disease progression can lead to death beforeY. pestisinfection can be diagnosed and treated. Usingin vivoanalyses and focusing on relevant cell types during pneumonic plague infection, we can identify host pathways that may be manipulated to extend the treatment window for pneumonic plague patients.

scholarly journals Identification of Biomarkers for Systemic Distribution of Nanovesicles From Lactobacillus johnsonii N6.2

2021 ◽  
Vol 12 ◽  
Author(s):  
Natalie A. Harrison ◽  
Christopher L. Gardner ◽  
Danilo R. da Silva ◽  
Claudio F. Gonzalez ◽  
Graciela L. Lorca
Keyword(s):  
Immune Modulation ◽  
Lactobacillus Johnsonii ◽  
Immunogold Staining ◽  
Intracellular Space ◽  
Host Interactions ◽  
Systemic Distribution ◽  
Significant Enrichment ◽  
Microbe Interactions ◽  
Host Microbe Interactions

The ability of bacterial extracellular vesicles (EV) to transport biological molecules has increased the research to determine their potential as therapeutic agents. In this study, Lactobacillus johnsonii N6.2-derived nanovesicles (NV) were characterized to identify components that may serve as biomarkers in host-microbe interactions. Comparative proteomic and lipidomic analyses of L. johnsonii N6.2 NV and cell membrane (CM) were performed. The lipidomic profiles indicated that both fractions contained similar lipids, however, significant differences were observed in several classes. LC-MS/MS proteomic analysis indicated that NV contained several unique and differentially expressed proteins when compared to the CM. Analysis of Gene Ontology (GO) terms, based on cellular component, showed significant enrichment of proteins in the cytoplasm/intracellular space category for the NV fraction. Based on these results, the proteins T285_RS00825 (named Sdp), Eno3 and LexA were selected for studies of localization and as potential biomarkers for host-microbe interactions. Immunogold staining, followed by scanning and transmission electron microscopy (SEM and TEM, respectively), revealed that Sdp was preferentially localized along the cell wall/membrane, and on NV-like structures surrounding the bacteria. These results were confirmed using immunofluorescence staining in Caco-2 cells incubated with NV. Consequently, we evaluated the potential for NV surface-exposed proteins to generate an immune response in the host. Plasma from individuals administered L. johnsonii N6.2 showed that IgA and IgG antibodies were generated against NV and Sdp domains in vivo. Altogether, these results show that L. johnsonii N6.2 NV have the potential to mediate host interactions through immune modulation.

scholarly journals Functions of Sphingolipids in Pathogenesis During Host–Pathogen Interactions

2021 ◽  
Vol 12 ◽  
Author(s):  
Jian Wang ◽  
Yi-Li Chen ◽  
Yong-Kang Li ◽  
Ding-Kang Chen ◽  
Jia-Fan He ◽  
...  
Keyword(s):  
Membrane Lipids ◽  
Host Factors ◽  
Bioactive Molecules ◽  
Microbial Pathogens ◽  
Microbial Pathogenesis ◽  
Host Interactions ◽  
Current State ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Host Metabolism

Sphingolipids are a class of membrane lipids that serve as vital structural and signaling bioactive molecules in organisms ranging from yeast to animals. Recent studies have emphasized the importance of sphingolipids as signaling molecules in the development and pathogenicity of microbial pathogens including bacteria, fungi, and viruses. In particular, sphingolipids play key roles in regulating the delicate balance between microbes and hosts during microbial pathogenesis. Some pathogens, such as bacteria and viruses, harness host sphingolipids to promote development and infection, whereas sphingolipids from both the host and pathogen are involved in fungus–host interactions. Moreover, a regulatory role for sphingolipids has been described, but their effects on host physiology and metabolism remain to be elucidated. Here, we summarize the current state of knowledge about the roles of sphingolipids in pathogenesis and interactions with host factors, including how sphingolipids modify pathogen and host metabolism with a focus on pathogenesis regulators and relevant metabolic enzymes. In addition, we discuss emerging perspectives on targeting sphingolipids that function in host–microbe interactions as new therapeutic strategies for infectious diseases.

scholarly journals Microbe-Host Communication by Small RNAs in Extracellular Vesicles: Vehicles for Transkingdom RNA Transportation

2019 ◽  
Vol 20 (6) ◽  
pp. 1487 ◽  
Author(s):  
Heon-Jin Lee
Keyword(s):  
Extracellular Vesicles ◽  
Small Rnas ◽  
Cell Communication ◽  
Cell Types ◽  
Eukaryotic Cells ◽  
Biological Research ◽  
Interspecies Communication ◽  
Microbe Interactions ◽  
Multiple Cell ◽  
Host Microbe Interactions

Extracellular vesicles (EVs) are evolutionary well-conserved nano-sized membranous vesicles that are secreted by both prokaryotic and eukaryotic cells. Recently, they have gained great attention for their proposed roles in cell-to-cell communication, and as biomarkers for human disease. In particular, small RNAs (sRNAs) contained within EVs have been considered as candidate interspecies-communication molecules, due to their demonstrated capacity to modulate gene expression in multiple cell types and species. While research into this field is in its infancy, elucidating the mechanisms that underlie host–microbe interactions and communications promises to impact many fields of biological research, including human health and medicine. Thus, this review discussed the results of recent studies that have examined the ways in which EVs and sRNAs mediate ‘microbe–host’ and ‘host–microbe’ interspecies communication.

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