scholarly journals Social interaction-induced activation of RNA splicing in the amygdala of microbiome-deficient mice

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Roman M Stilling ◽  
Gerard M Moloney ◽  
Feargal J Ryan ◽  
Alan E Hoban ◽  
Thomaz FS Bastiaanssen ◽  
...  
Keyword(s):  
Social Interaction ◽  
Social Behaviour ◽  
Rna Splicing ◽  
Molecular Mechanisms ◽  
Autism Spectrum ◽  
Gene Expression Response ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Expression Response ◽  
Multiple Species

Social behaviour is regulated by activity of host-associated microbiota across multiple species. However, the molecular mechanisms mediating this relationship remain elusive. We therefore determined the dynamic, stimulus-dependent transcriptional regulation of germ-free (GF) and GF mice colonised post weaning (exGF) in the amygdala, a brain region critically involved in regulating social interaction. In GF mice the dynamic response seen in controls was attenuated and replaced by a marked increase in expression of splicing factors and alternative exon usage in GF mice upon stimulation, which was even more pronounced in exGF mice. In conclusion, we demonstrate a molecular basis for how the host microbiome is crucial for a normal behavioural response during social interaction. Our data further suggest that social behaviour is correlated with the gene-expression response in the amygdala, established during neurodevelopment as a result of host-microbe interactions. Our findings may help toward understanding neurodevelopmental events leading to social behaviour dysregulation, such as those found in autism spectrum disorders (ASDs).

scholarly journals A New C-Type Lectin Similar to the Human Immunoreceptor DC-SIGN Mediates Symbiont Acquisition by a Marine Nematode

2006 ◽  
Vol 72 (4) ◽  
pp. 2950-2956 ◽  
Author(s):  
Silvia Bulgheresi ◽  
Irma Schabussova ◽  
Tie Chen ◽  
Nicholas P. Mullin ◽  
Rick M. Maizels ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Marine Nematode ◽  
Mannose Binding Protein ◽  
Mannose Binding ◽  
Marine Symbiosis ◽  
Microbe Interactions ◽  
Sulfur Oxidizing ◽  
Host Microbe Interactions ◽  
Symbiont Acquisition

ABSTRACT Although thiotrophic symbioses have been intensively studied for the last three decades, nothing is known about the molecular mechanisms of symbiont acquisition. We used the symbiosis between the marine nematode Laxus oneistus and sulfur-oxidizing bacteria to study this process. In this association a monolayer of symbionts covers the whole cuticle of the nematode, except its anterior-most region. Here, we identify a novel Ca2+-dependent mannose-specific lectin that was exclusively secreted onto the posterior, bacterium-associated region of L. oneistus cuticle. A recombinant form of this lectin induced symbiont aggregation in seawater and was able to compete with the native lectin for symbiont binding in vivo. Surprisingly, the carbohydrate recognition domain of this mannose-binding protein was similar both structurally and functionally to a human dendritic cell-specific immunoreceptor. Our results provide a molecular link between bacterial symbionts and host-secreted mucus in a marine symbiosis and suggest conservation in the mechanisms of host-microbe interactions throughout the animal kingdom.

scholarly journals Tolerogenic transcriptome landscape in CD8+ T lymphocytes after exposure to erythrocyte-targeted antigens

2018 ◽  
Author(s):  
Alizée J. Grimm ◽  
Cédric Gobet ◽  
Giacomo Diaceri ◽  
Xavier Quaglia-Thermes ◽  
Jeffrey A. Hubbell
Keyword(s):  
T Cells ◽  
T Cell ◽  
Molecular Mechanisms ◽  
Tolerance Induction ◽  
Peripheral Tolerance ◽  
Response To Treatment ◽  
Gene Expression Response ◽  
Genes Encoding ◽  
Expression Response ◽  
T Cell Phenotypes

AbstractOur group has recently shown induction of antigen-specific T cell tolerance through targeting of the antigen to erythrocytes in situ. The tolerogenic state is characterized by initial proliferation of antigen-specific T cells and subsequent acquisition of signatures associated with both deletional, anergic and regulatory T cell phenotypes. In this study we wished to further understand the molecular mechanisms behind induction of tolerance by erythrocyte-targeted antigens. RNA sequencing was performed to determine how gene expression response is regulated in tolerized ovalbumin-specific CD8+ T cells and which molecular pathways are activated after treatment with this technology. Treatment with erythrocyte-targeted antigens led to the upregulation of genes encoding several TCR co-inhibitory receptors such as CTLA4, PD1, LAG3, TIGIT and CD200R1, and lack of upregulation of cytotoxic and pro-inflammatory signaling molecule genes. Modulation in expression of the master transcription factors Egr2/NFatc1, Nur77 family and E2f1 was also observed, all known to be associated with the natural process of establishment of peripheral tolerance. Expression of these genes differed in response to treatment with soluble ovalbumin or SIINFEKL MHCI peptide, suggesting a specific mechanism of T cell modulation and tolerance induction in response to the erythrocyte-associated forms.

scholarly journals Spatial Analyses of Specialized Metabolites: The Key to Studying Function in Hosts

mSystems ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Melissa M. Galey ◽  
Laura M. Sanchez
Keyword(s):  
Analytical Chemistry ◽  
Molecular Mechanisms ◽  
Imaging Mass Spectrometry ◽  
Analytical Techniques ◽  
Spatial Analyses ◽  
Biological Functions ◽  
Specialized Metabolites ◽  
Microbe Interactions ◽  
Host Microbe Interactions

ABSTRACT Microbial communities contribute to a wide variety of biological functions in hosts and have the ability to specifically influence the health of those organisms through production of specialized metabolites. However, the structures or molecular mechanisms related to health or disease in host-microbe interactions represent a knowledge gap. In order to close this gap, we propose that a combinatory approach, pulling from microbiology and analytical chemistry, be considered to investigate these interactions so as to gain a better understanding of the chemistry being produced. We hypothesize that bacteria alter their chemistry in order to survive and induce specific states in their host organisms. Our lab makes use of imaging mass spectrometry and other analytical techniques to study this chemistry in situ , which provides actionable information to test hypotheses.

Bacterial receptors for host transferrin and lactoferrin: molecular mechanisms and role in host–microbe interactions

2013 ◽  
Vol 8 (12) ◽  
pp. 1575-1585 ◽  
Author(s):  
Ari Morgenthau ◽  
Anastassia Pogoutse ◽  
Paul Adamiak ◽  
Trevor F Moraes ◽  
Anthony B Schryvers
Keyword(s):  
Molecular Mechanisms ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Bacterial Receptors

scholarly journals Interplays between human microbiota and microRNAs in COVID-19 pathogenesis: a literature review

2021 ◽  
Vol 25 (2) ◽  
pp. 1-7
Author(s):  
Bok Sil Hong ◽  
Myoung-Ryu Kim
Keyword(s):  
Molecular Mechanisms ◽  
Host Immune System ◽  
Host Gene Expression ◽  
Human Microbiota ◽  
Inflammatory Status ◽  
Bidirectional Association ◽  
Comprehensive Picture ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Gut Microbiota Composition

[Purpose] Recent studies have shown that COVID-19 is often associated with altered gut microbiota composition and reflects disease severity. Furthermore, various reports suggest that the interaction between COVID-19 and host-microbiota homeostasis is mediated through the modulation of microRNAs (miRNAs). Thus, in this review, we aim to summarize the association between human microbiota and miRNAs in COVID-19 pathogenesis.[Methods] We searched for the existing literature using the keywords such “COVID-19 or microbiota,” “microbiota or microRNA,” and “COVID-19 or probiotics” in PubMed until March 31, 2021. Subsequently, we thoroughly reviewed the articles related to microbiota and miRNAs in COVID-19 to generate a comprehensive picture depicting the association between human microbiota and microRNAs in the pathogenesis of COVID-19.[Results] There exists strong experimental evidence suggesting that the composition and diversity of human microbiota are altered in COVID-19 patients, implicating a bidirectional association between the respiratory and gastrointestinal tracts. In addition, SARS-CoV-2 encoded miRNAs and host cellular microRNAs modulated by human microbiota can interfere with viral replication and regulate host gene expression involved in the initiation and progression of COVID-19. These findings suggest that the manipulation of human microbiota with probiotics may play a significant role against SARS-CoV-2 infection by enhancing the host immune system and lowering the inflammatory status.[Conclusion] The human microbiota-miRNA axis can be used as a therapeutic approach for COVID-19. Hence, further studies are needed to investigate the exact molecular mechanisms underlying the regulation of miRNA expression in human microbiota and how these miRNA profiles mediate viral infection through host-microbe interactions.

scholarly journals Probiotics and MicroRNA: Their Roles in the Host–Microbe Interactions

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Zhao ◽  
Yan Zeng ◽  
Dong Zeng ◽  
Hesong Wang ◽  
Mengjia Zhou ◽  
...  
Keyword(s):  
Disease Management ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Comprehensive Description ◽  
Future Studies ◽  
Gut Homeostasis ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Gut Microorganisms

Probiotics are widely accepted to be beneficial for the maintenance of the gut homeostasis – the dynamic and healthy interactions between host and gut microorganisms. In addition, emerging as a key molecule of inter-domain communication, microRNAs (miRNAs) can also mediate the host–microbe interactions. However, a comprehensive description and summary of the association between miRNAs and probiotics have not been reported yet. In this review, we have discussed the roles of probiotics and miRNAs in host–microbe interactions and proposed the association of probiotics with altered miRNAs in various intestinal diseases and potential molecular mechanisms underlying the action of probiotics. Furthermore, we provided a perspective of probiotics–miRNA–host/gut microbiota axis applied in search of disease management highly associated with the gut microbiome, which will potentially prove to be beneficial for future studies.

scholarly journals In vitro cell and tissue models for studying host–microbe interactions: a review

2013 ◽  
Vol 109 (S2) ◽  
pp. S27-S34 ◽  
Author(s):  
Miriam Bermudez-Brito ◽  
Julio Plaza-Díaz ◽  
Luis Fontana ◽  
Sergio Muñoz-Quezada ◽  
Angel Gil
Keyword(s):  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Experimental Models ◽  
Dynamic Interactions ◽  
Basolateral Side ◽  
Microbe Interactions ◽  
Host Microbe Interactions

Ideally, cell models should resemble the in vivo conditions; however, in most in vitro experimental models, epithelial cells are cultivated as monolayers, in which the establishment of functional epithelial features is not achieved. To overcome this problem, co-culture experiments with probiotics, dendritic cells and intestinal epithelial cells and three-dimensional models attempt to reconcile the complex and dynamic interactions that exist in vivo between the intestinal epithelium and bacteria on the luminal side and between the epithelium and the underlying immune system on the basolateral side. Additional models include tissue explants, bioreactors and organoids. The present review details the in vitro models used to study host–microbe interactions and explores the new tools that may help in understanding the molecular mechanisms of these interactions.

scholarly journals Evolution Shapes the Gene Expression Response to Oxidative Stress

2019 ◽  
Vol 20 (12) ◽  
pp. 3040 ◽  
Author(s):  
Rima Siauciunaite ◽  
Nicholas S. Foulkes ◽  
Viola Calabrò ◽  
Daniela Vallone
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Molecular Mechanisms ◽  
Survival Strategies ◽  
Cell Physiology ◽  
Gene Expression Response ◽  
Low Levels ◽  
Expression Response ◽  
Species Specific ◽  
And Function

Reactive oxygen species (ROS) play a key role in cell physiology and function. ROS represents a potential source of damage for many macromolecules including DNA. It is thought that daily changes in oxidative stress levels were an important early factor driving evolution of the circadian clock which enables organisms to predict changes in ROS levels before they actually occur and thereby optimally coordinate survival strategies. It is clear that ROS, at relatively low levels, can serve as an important signaling molecule and also serves as a key regulator of gene expression. Therefore, the mechanisms that have evolved to survive or harness these effects of ROS are ancient evolutionary adaptations that are tightly interconnected with most aspects of cellular physiology. Our understanding of these mechanisms has been mainly based on studies using a relatively small group of genetic models. However, we know comparatively little about how these mechanisms are conserved or have adapted during evolution under different environmental conditions. In this review, we describe recent work that has revealed significant species-specific differences in the gene expression response to ROS by exploring diverse organisms. This evidence supports the notion that during evolution, rather than being highly conserved, there is inherent plasticity in the molecular mechanisms responding to oxidative stress.

scholarly journals PP4-dependent HDAC3 dephosphorylation discriminates between axonal regeneration and regenerative failure

2018 ◽  
Author(s):  
Arnau Hervera ◽  
Luming Zhou ◽  
Ilaria Palmisano ◽  
Eilidh McLachlan ◽  
Guiping Kong ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Spinal Injury ◽  
Gene Expression Response ◽  
Cord Injury ◽  
Expression Response

The molecular mechanisms discriminating between regenerative failure and success remain elusive. While a regeneration-competent peripheral nerve injury mounts a regenerative gene expression response in bipolar dorsal root ganglia (DRG) sensory neurons, a regeneration-incompetent central spinal cord injury does not. This dichotomic response offers a unique opportunity to investigate the fundamental biological mechanisms underpinning regenerative ability. Following a pharmacological screen with small molecule inhibitors targeting key epigenetic enzymes in DRG neurons we identified HDAC3 signalling as a novel candidate brake to axonal regenerative growth. In vivo, we determined that only a regenerative peripheral but not a central spinal injury induces an increase in calcium, which activates protein phosphatase 4 that in turn dephosphorylates HDAC3 thus impairing its activity and enhancing histone acetylation. Bioinformatics analysis of ex vivo H3K9ac ChIPseq and RNAseq from DRG followed by promoter acetylation and protein expression studies implicated HDAC3 in the regulation of multiple regenerative pathways. Finally, genetic or pharmacological HDAC3 inhibition overcame regenerative failure of sensory axons following spinal cord injury. Together, these data indicate that PP4-dependent HDAC3 dephosphorylation discriminates between axonal regeneration and regenerative failure.

scholarly journals Xenorhabdus nematophilus as a Model for Host-Bacterium Interactions: rpoS Is Necessary for Mutualism with Nematodes

2001 ◽  
Vol 183 (16) ◽  
pp. 4687-4693 ◽  
Author(s):  
Eugenio I. Vivas ◽  
Heidi Goodrich-Blair
Keyword(s):  
Molecular Mechanisms ◽  
Host Bacterium ◽  
Gram Negative ◽  
Host Interactions ◽  
Specific Allele ◽  
Microbe Interactions ◽  
Xenorhabdus Nematophilus ◽  
Host Microbe Interactions ◽  
Wild Type Parent

ABSTRACT Xenorhabdus nematophilus, a gram-negative bacterium, is a mutualist of Steinernema carpocapsae nematodes and a pathogen of larval-stage insects. We use this organism as a model of host-microbe interactions to identify the functions bacteria require for mutualism, pathogenesis, or both. In many gram-negative bacteria, the transcription factor ςS controls regulons that can mediate stress resistance, survival, or host interactions. Therefore, we examined the role of ςS in the ability of X. nematophilus to interact with its hosts. We cloned, sequenced, and disrupted the X. nematophilus rpoS gene that encodes ςS. The X. nematophilus rpoS mutant pathogenized insects as well as its wild-type parent. However, therpoS mutant could not mutualistically colonize nematode intestines. To our knowledge, this is the first report of a specific allele that affects the ability of X. nematophilus to exist within nematode intestines, an important step in understanding the molecular mechanisms of this association.

Sign in / Sign up

Export Citation Format

Share Document