scholarly journals Host Immunity Alters Community Ecology and Stability of the Microbiome in a Caenorhabditis elegans Model

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Megan Taylor ◽  
N. M. Vega
Keyword(s):  
Innate Immunity ◽  
Caenorhabditis Elegans ◽  
Community Ecology ◽  
Community Composition ◽  
Host Immunity ◽  
Interspecies Interactions ◽  
Ecological Processes ◽  
Content Type ◽  
Microbiome Composition ◽  
Insulin Growth Factor

ABSTRACT A growing body of data suggests that the microbiome of a species can vary considerably from individual to individual, but the reasons for this variation—and the consequences for the ecology of these communities—remain only partially explained. In mammals, the emerging picture is that the metabolic state and immune system status of the host affect the composition of the microbiome, but quantitative ecological microbiome studies are challenging to perform in higher organisms. Here, we show that these phenomena can be quantitatively analyzed in the tractable nematode host Caenorhabditis elegans. Mutants in innate immunity, in particular the DAF-2/insulin growth factor (IGF) pathway, are shown to contain a microbiome that differs from that of wild-type nematodes. We analyzed the underlying basis of these differences from the perspective of community ecology by comparing experimental observations to the predictions of a neutral sampling model and concluded that fundamental differences in microbiome ecology underlie the observed differences in microbiome composition. We tested this hypothesis by introducing a minor perturbation into the colonization conditions, allowing us to assess stability of communities in different host strains. Our results show that altering host immunity changes the importance of interspecies interactions within the microbiome, resulting in differences in community composition and stability that emerge from these differences in host-microbe ecology. IMPORTANCE Here, we used a Caenorhabditis elegans microbiome model to demonstrate how genetic differences in innate immunity alter microbiome composition, diversity, and stability by changing the ecological processes that shape these communities. These results provide insight into the role of host genetics in controlling the ecology of the host-associated microbiota, resulting in differences in community composition, successional trajectories, and response to perturbation.

scholarly journals Host immunity alters successional ecology and stability of the microbiome in a C. elegans model

2020 ◽  
Author(s):  
Megan Taylor ◽  
NM Vega
Keyword(s):  
Innate Immunity ◽  
Caenorhabditis Elegans ◽  
Community Composition ◽  
Species Interactions ◽  
Host Immunity ◽  
Ecological Processes ◽  
Microbiome Composition ◽  
C Elegans ◽  
Insulin Growth Factor ◽  
A Minor

AbstractA growing body of data suggests that the microbiome of a species can vary considerably from individual to individual, but the reasons for this variation - and the consequences for the ecology of these communities – remain only partially explained. In mammals, the emerging picture is that the metabolic state and immune system status of the host affects the composition of the microbiome, but quantitative ecological microbiome studies are challenging to perform in higher organisms. Here we show that these phenomena can be quantitatively analyzed in the tractable nematode host Caenorhabditis elegans. Mutants in innate immunity, in particular the DAF-2/Insulin Growth Factor (IGF) pathway, are shown to contain a microbiome that differs from that of wild type nematodes. We analyze the underlying basis of these differences from the perspective of community ecology by comparing experimental observations to the predictions of a neutral sampling model and conclude that fundamental differences in microbiome ecology underlie the observed differences in microbiome composition. We test this hypothesis by introducing a minor perturbation to the colonization conditions, allowing us to assess stability of communities in different host strains. Our results show that altering host immunity changes the importance of inter-species interactions within the microbiome, resulting in differences in community composition and stability that emerge from these differences in host-microbe ecology.ImportanceHere we use a Caenorhabditis elegans microbiome model to demonstrate how genetic differences in innate immunity alter microbiome composition, diversity, and stability by changing the ecological processes that shape these communities. These results provide insight into the role of host genetics in controlling the ecology of host-associated microbiota, resulting in differences in community composition, successional trajectories, and response to perturbation.

Take a Walk to the Wild Side of Caenorhabditis elegans-Pathogen Interactions

2021 ◽  
Vol 85 (2) ◽  
Author(s):  
Leah J. Radeke ◽  
Michael A. Herman
Keyword(s):  
Innate Immunity ◽  
Caenorhabditis Elegans ◽  
Recent Work ◽  
Genetic Model ◽  
Model Organism ◽  
Bacterial Pathogen ◽  
Content Type ◽  
Microbiome Composition ◽  
C Elegans ◽  
Functional Studies

SUMMARY Microbiomes form intimate functional associations with their hosts. Much has been learned from correlating changes in microbiome composition to host organismal functions. However, in-depth functional studies require the manipulation of microbiome composition coupled with the precise interrogation of organismal physiology—features available in few host study systems. Caenorhabditis elegans has proven to be an excellent genetic model organism to study innate immunity and, more recently, microbiome interactions. The study of C. elegans-pathogen interactions has provided in depth understanding of innate immune pathways, many of which are conserved in other animals. However, many bacteria were chosen for these studies because of their convenience in the lab setting or their implication in human health rather than their native interactions with C. elegans. In their natural environment, C. elegans feed on a variety of bacteria found in rotting organic matter, such as rotting fruits, flowers, and stems. Recent work has begun to characterize the native microbiome and has identified a common set of bacteria found in the microbiome of C. elegans. While some of these bacteria are beneficial to C. elegans health, others are detrimental, leading to a complex, multifaceted understanding of bacterium-nematode interactions. Current research on nematode-bacterium interactions is focused on these native microbiome components, both their interactions with each other and with C. elegans. We will summarize our knowledge of bacterial pathogen-host interactions in C. elegans, as well as recent work on the native microbiome, and explore the incorporation of these bacterium-nematode interactions into studies of innate immunity and pathogenesis.

scholarly journals Octopaminergic Signaling Mediates Neural Regulation of Innate Immunity in Caenorhabditis elegans

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Durai Sellegounder ◽  
Chung-Hsiang Yuan ◽  
Phillip Wibisono ◽  
Yiyong Liu ◽  
Jingru Sun
Keyword(s):  
Innate Immunity ◽  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Immune Responses ◽  
Human Health ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Pathogen Infection ◽  
Content Type ◽  
Immunological Homeostasis

ABSTRACT Upon pathogen infection, the nervous system regulates innate immunity to confer coordinated protection to the host. However, the precise mechanisms of such regulation remain unclear. Previous studies have demonstrated that OCTR-1, a putative G protein-coupled receptor for catecholamine, functions in the sensory neurons designated “ASH” to suppress innate immune responses in Caenorhabditis elegans. It is unknown what molecules act as OCTR-1 ligands in the neural immune regulatory circuit. Here we identify neurotransmitter octopamine (OA) as an endogenous ligand for OCTR-1 in immune regulation and show that the OA-producing RIC neurons function in the OCTR-1 neural circuit to suppress innate immunity. RIC neurons are deactivated in the presence of pathogens but transiently activated by nonpathogenic bacteria. Our data support a model whereby an octopaminergic immunoinhibitory pathway is tonically active under normal conditions to maintain immunological homeostasis or suppress unwanted innate immune responses but downregulated upon pathogen infection to allow enhanced innate immunity. As excessive innate immune responses have been linked to a myriad of human health concerns, our study could potentially benefit the development of more-effective treatments for innate immune disorders. IMPORTANCE Insufficient or excessive immune responses to pathogen infection are major causes of disease. Increasing evidence indicates that the nervous system regulates the immune system to help maintain immunological homeostasis. However, the precise mechanisms of this regulation are largely unknown. Here we show the existence of an octopaminergic immunoinhibitory pathway in Caenorhabditis elegans. Our study results indicate that this pathway is tonically active under normal conditions to maintain immunological homeostasis or suppress unwanted innate immune responses but downregulated upon pathogen infection to allow enhanced innate immunity. As excessive innate immune responses have been linked to human health conditions such as Crohn's disease, rheumatoid arthritis, atherosclerosis, diabetes, and Alzheimer's disease, elucidating octopaminergic neural regulation of innate immunity could be helpful in the development of new treatments for innate immune diseases.

scholarly journals New Role for DCR-1/Dicer in Caenorhabditis elegans Innate Immunity against the Highly Virulent Bacterium Bacillus thuringiensis DB27

2013 ◽  
Vol 81 (10) ◽  
pp. 3942-3957 ◽  
Author(s):  
Igor Iatsenko ◽  
Amit Sinha ◽  
Christian Rödelsperger ◽  
Ralf J. Sommer
Keyword(s):  
Innate Immunity ◽  
Caenorhabditis Elegans ◽  
Bacillus Thuringiensis ◽  
Defense Mechanisms ◽  
Content Type ◽  
Mirna Processing ◽  
C Elegans ◽  
Nuclear Autoantigenic Sperm Protein ◽  
Bacterium Bacillus ◽  
Underlying Mechanisms

ABSTRACTBacillus thuringiensisproduces toxins that target invertebrates, includingCaenorhabditis elegans. Virulence ofBacillusstrains is often highly specific, such thatB. thuringiensisstrain DB27 is highly pathogenic toC. elegansbut shows no virulence for another model nematode,Pristionchus pacificus. To uncover the underlying mechanisms of the differential responses of the two nematodes toB. thuringiensisDB27 and to reveal theC. elegansdefense mechanisms against this pathogen, we conducted a genetic screen forC. elegansmutants resistant toB. thuringiensisDB27. Here, we describe aB. thuringiensisDB27-resistantC. elegansmutant that is identical tonasp-1, which encodes theC. eleganshomolog of the nuclear-autoantigenic-sperm protein. Gene expression analysis indicated a substantial overlap between the genes downregulated in thenasp-1mutant and targets ofC. elegansdcr-1/Dicer, suggesting thatdcr-1is repressed innasp-1mutants, which was confirmed by quantitative PCR. Consistent with this, thenasp-1mutant exhibits RNA interference (RNAi) deficiency and reduced longevity similar to those of adcr-1mutant. Building on these surprising findings, we further explored a potential role fordcr-1inC. elegansinnate immunity. We show thatdcr-1mutant alleles deficient in microRNA (miRNA) processing, but not those deficient only in RNAi, are resistant toB. thuringiensisDB27. Furthermore,dcr-1overexpression rescues thenasp-1mutant's resistance, suggesting that repression ofdcr-1determines thenasp-1mutant's resistance. Additionally, we identified the collagen-encoding genecol-92as one of the downstream effectors ofnasp-1that play an important role in resistance to DB27. Taken together, these results uncover a previously unknown role for DCR-1/Dicer inC. elegansantibacterial immunity that is largely associated with miRNA processing.

scholarly journals Pseudomonas aeruginosa PA14 Enhances the Efficacy of Norfloxacin against Staphylococcus aureus Newman Biofilms

2020 ◽  
Vol 202 (18) ◽  
Author(s):  
Giulia Orazi ◽  
Fabrice Jean-Pierre ◽  
George A. O’Toole
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Respiratory Infections ◽  
Multiple Infection ◽  
Bacterial Biofilms ◽  
Interspecies Interactions ◽  
Chronic Infections ◽  
Content Type

ABSTRACT The thick mucus within the airways of individuals with cystic fibrosis (CF) promotes frequent respiratory infections that are often polymicrobial. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent pathogens that cause CF pulmonary infections, and both are among the most common etiologic agents of chronic wound infections. Furthermore, the ability of P. aeruginosa and S. aureus to form biofilms promotes the establishment of chronic infections that are often difficult to eradicate using antimicrobial agents. In this study, we found that multiple LasR-regulated exoproducts of P. aeruginosa, including 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), siderophores, phenazines, and rhamnolipids, likely contribute to the ability of P. aeruginosa PA14 to shift S. aureus Newman norfloxacin susceptibility profiles. Here, we observe that exposure to P. aeruginosa exoproducts leads to an increase in intracellular norfloxacin accumulation by S. aureus. We previously showed that P. aeruginosa supernatant dissipates the S. aureus membrane potential, and furthermore, depletion of the S. aureus proton motive force recapitulates the effect of the P. aeruginosa PA14 supernatant on shifting norfloxacin sensitivity profiles of biofilm-grown S. aureus Newman. From these results, we hypothesize that exposure to P. aeruginosa PA14 exoproducts leads to increased uptake of the drug and/or an impaired ability of S. aureus Newman to efflux norfloxacin. Surprisingly, the effect observed here of P. aeruginosa PA14 exoproducts on S. aureus Newman susceptibility to norfloxacin seemed to be specific to these strains and this antibiotic. Our results illustrate that microbially derived products can alter the ability of antimicrobial agents to kill bacterial biofilms. IMPORTANCE Pseudomonas aeruginosa and Staphylococcus aureus are frequently coisolated from multiple infection sites, including the lungs of individuals with cystic fibrosis (CF) and nonhealing diabetic foot ulcers. Coinfection with P. aeruginosa and S. aureus has been shown to produce worse outcomes compared to infection with either organism alone. Furthermore, the ability of these pathogens to form biofilms enables them to cause persistent infection and withstand antimicrobial therapy. In this study, we found that P. aeruginosa-secreted products dramatically increase the ability of the antibiotic norfloxacin to kill S. aureus biofilms. Understanding how interspecies interactions alter the antibiotic susceptibility of bacterial biofilms may inform treatment decisions and inspire the development of new therapeutic strategies.

scholarly journals Function of the Pyruvate Oxidase-Lactate Oxidase Cascade in Interspecies Competition between Streptococcus oligofermentans and Streptococcus mutans

2012 ◽  
Vol 78 (7) ◽  
pp. 2120-2127 ◽  
Author(s):  
Lei Liu ◽  
Huichun Tong ◽  
Xiuzhu Dong
Keyword(s):  
Stationary Phase ◽  
Streptococcus Mutans ◽  
Growth Phase ◽  
Large Degree ◽  
Interspecies Interactions ◽  
Lactate Oxidase ◽  
Interspecies Competition ◽  
Pyruvate Oxidase ◽  
Content Type

ABSTRACTComplex interspecies interactions occur constantly between oral commensals and the opportunistic pathogenStreptococcus mutansin dental plaque. Previously, we showed that oral commensalStreptococcus oligofermentanspossesses multiple enzymes for H2O2production, especially lactate oxidase (Lox), allowing it to out-competeS. mutans. In this study, through extensive biochemical and genetic studies, we identified a pyruvate oxidase (pox) gene inS. oligofermentans. Apoxdeletion mutant completely lost Pox activity, while ectopically expressedpoxrestored activity. Pox was determined to produce most of the H2O2in the earlier growth phase and log phase, while Lox mainly contributed to H2O2production in stationary phase. Bothpoxandloxwere expressed throughout the growth phase, while expression of theloxgene increased by about 2.5-fold when cells entered stationary phase. Since lactate accumulation occurred to a large degree in stationary phase, the differential Pox- and Lox-generated H2O2can be attributed to differential gene expression and substrate availability. Interestingly, inactivation ofpoxcauses a dramatic reduction in H2O2production from lactate, suggesting a synergistic action of the two oxidases in converting lactate into H2O2. In anin vitrotwo-species biofilm experiment, thepoxmutant ofS. oligofermentansfailed to inhibitS. mutanseven thoughloxwas active. In summary,S. oligofermentansdevelops a Pox-Lox synergy strategy to maximize its H2O2formation so as to win the interspecies competition.

scholarly journals The community ecology of pathogens: coinfection, coexistence and community composition

2015 ◽  
Vol 18 (4) ◽  
pp. 401-415 ◽  
Author(s):  
Eric W. Seabloom ◽  
Elizabeth T. Borer ◽  
Kevin Gross ◽  
Amy E. Kendig ◽  
Christelle Lacroix ◽  
...  
Keyword(s):  
Community Ecology ◽  
Community Composition

scholarly journals Immune Gene Expression Covaries with Gut Microbiome Composition in Stickleback

mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Lauren E. Fuess ◽  
Stijn den Haan ◽  
Fei Ling ◽  
Jesse N. Weber ◽  
Natalie C. Steinel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microbial Communities ◽  
Gut Microbiome ◽  
Alpha Diversity ◽  
Host Immunity ◽  
Host Gene ◽  
Microbiota Composition ◽  
Host Gene Expression ◽  
Microbiome Composition ◽  
Immune Genes

ABSTRACT Commensal microbial communities have immense effects on their vertebrate hosts, contributing to a number of physiological functions, as well as host fitness. In particular, host immunity is strongly linked to microbiota composition through poorly understood bi-directional links. Gene expression may be a potential mediator of these links between microbial communities and host function. However, few studies have investigated connections between microbiota composition and expression of host immune genes in complex systems. Here, we leverage a large study of laboratory-raised fish from the species Gasterosteus aculeatus (three-spined stickleback) to document correlations between gene expression and microbiome composition. First, we examined correlations between microbiome alpha diversity and gene expression. Our results demonstrate robust positive associations between microbial alpha diversity and expression of host immune genes. Next, we examined correlations between host gene expression and abundance of microbial taxa. We identified 15 microbial families that were highly correlated with host gene expression. These families were all tightly correlated with host expression of immune genes and processes, falling into one of three categories—those positively correlated, negatively correlated, and neutrally related to immune processes. Furthermore, we highlight several important immune processes that are commonly associated with the abundance of these taxa, including both macrophage and B cell functions. Further functional characterization of microbial taxa will help disentangle the mechanisms of the correlations described here. In sum, our study supports prevailing hypotheses of intimate links between host immunity and gut microbiome composition. IMPORTANCE Here, we document associations between host gene expression and gut microbiome composition in a nonmammalian vertebrate species. We highlight associations between expression of immune genes and both microbiome diversity and abundance of specific microbial taxa. These findings support other findings from model systems which have suggested that gut microbiome composition and host immunity are intimately linked. Furthermore, we demonstrate that these correlations are truly systemic; the gene expression detailed here was collected from an important fish immune organ (the head kidney) that is anatomically distant from the gut. This emphasizes the systemic impact of connections between gut microbiota and host immune function. Our work is a significant advancement in the understanding of immune-microbiome links in nonmodel, natural systems.

Sign in / Sign up

Export Citation Format

Share Document