Harnessing the microbiome to regulate systemic innate immunity II
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1123664 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29397727_1.fastq.gz | Fastqsanger.gz | |||
| SRR29397727_2.fastq.gz | Fastqsanger.gz | |||
| SRR29397728_1.fastq.gz | Fastqsanger.gz | |||
| SRR29397728_2.fastq.gz | Fastqsanger.gz | |||
| SRR29397729_1.fastq.gz | Fastqsanger.gz |
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Project description:Harnessing the microbiome to regulate systemic innate immunity I
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Project description:Mechanisms through which the microbiome communicates with the systemic immune system remain unclear. We have identified a family of microbiome Bacteroidota-derived lipopeptides – the serine-glycine (S/G) lipids, and specifically L654 – that are TLR2 ligands, access the systemic circulation, and potentially link the microbiome and systemic innate immunity. We have previously postulated that L654 and the S/G lipids regulate systemic innate immunity by entering the systemic circulation and mediating weak TLR2 interactions that maintain “normal” levels of innate immune signaling feedback inhibitors. In proof-of-concept studies, we reported that increasing systemic L654 levels in mice by administering exogenous L654 intravenously significantly diminishes systemic innate immune responses and attenuates murine autoimmunity. In the present study, our goal was to confirm the role of the microbiome in mediating this mode of immunoregulation by decreasing the microbiome-based production of S/G lipids. We now report that decreasing microbiome Bacteroidota in mice using a specific oral antibiotic/rest protocol reduces fecal and plasma S/G lipids levels and significantly enhances systemic innate immune responses. Replenishing systemic levels of S/G lipids after antibiotic treatment through exogenous administration of L654 returns innate immune responses to normal levels, confirming the regulatory role of S/G lipids in this mode of microbiome regulation. Finally, RNAseq analysis of splenic monocytes derived from antibiotic-treated and control mice prior to ex vivo stimulation demonstrates that the antibiotic/rest protocol and the concomitant decrease in microbiome S/G lipids and Bacteroidota has significant downregulatory effects on normal homeostatic pro-inflammatory pathways. These effects are also associated with downregulation of specific proinflammatory pathway inhibitors, which may suggest a potential mechanism underlying the enhancement in ex vivo innate immune stimulated responses of these monocytes. Overall, our results suggest that S/G lipids are microbiome-derived bacterial factors capable of regulating systemic innate immunity and as such are manipulatable targets with therapeutic potential for enhancing or decreasing innate immunity in the context of infectious, malignant, and autoimmune diseases.
2024-06-12 | GSE236817 | GEO
Project description:Mechanisms through which the microbiome communicates with the systemic immune system remain unclear. We have identified a family of microbiome Bacteroidota-derived lipopeptides – the serine-glycine (S/G) lipids, and specifically L654 – that are TLR2 ligands, access the systemic circulation, and potentially link the microbiome and systemic innate immunity. We have previously postulated that L654 and the S/G lipids regulate systemic innate immunity by entering the systemic circulation and mediating weak TLR2 interactions that maintain “normal” levels of innate immune signaling feedback inhibitors. In proof-of-concept studies, we reported that increasing systemic L654 levels in mice by administering exogenous L654 intravenously significantly diminishes systemic innate immune responses and attenuates murine autoimmunity. In the present study, our goal was to confirm the role of the microbiome in mediating this mode of immunoregulation by decreasing the microbiome-based production of S/G lipids. We now report that decreasing microbiome Bacteroidota in mice using a specific oral antibiotic/rest protocol reduces fecal and plasma S/G lipids levels and significantly enhances systemic innate immune responses. Replenishing systemic levels of S/G lipids after antibiotic treatment through exogenous administration of L654 returns innate immune responses to normal levels, confirming the regulatory role of S/G lipids in this mode of microbiome regulation. Finally, RNAseq analysis of splenic monocytes derived from antibiotic-treated and control mice with or without exogenous L654 prior to ex vivo stimulation demonstrates that the antibiotic/rest protocol and the concomitant decrease in microbiome S/G lipids and Bacteroidota has significant downregulatory effects on normal homeostatic pro-inflammatory pathways. These effects are also associated with downregulation of specific proinflammatory pathway inhibitors, which may suggest a potential mechanism underlying the enhancement in ex vivo innate immune stimulated responses of these monocytes. Overall, our results suggest that S/G lipids are microbiome-derived bacterial factors capable of regulating systemic innate immunity and as such are manipulatable targets with therapeutic potential for enhancing or decreasing innate immunity in the context of infectious, malignant, and autoimmune diseases.
2024-06-20 | GSE269771 | GEO
Project description:Intercellular and systemic signalling is an essential hallmark of multicellular life. Encounter of pathogens occurs locally but triggers organ scale and organismic immune responses. In plants, elicitor perception provokes rapid, systemically expanding Ca2+ and H2O2 second messenger signals conferring innate immunity. However, the underlying components and mechanisms for enabling and sustaining signal propagation have remained elusive. Here, we report how plants achieve perpetuated Ca2+/H2O2 signal proliferation and simultaneously avoid disturbance of ongoing cellular signalling along the path of response dissemination. We identify a CBL1/CIPK26/CPK5 Ca2+ sensing/phosphorylation module from Arabidopsis thaliana as crucial for systemic signal propagation. This bi-kinase signalling module becomes Ca2+-sensitized and super-activated through mutual trans-phosphorylation and in consequence imposes a cooperative and enhanced phosphorylation pattern on the RBOHD NADPH oxidase causing maximized H2O2 generation. Biochemical, genetic and Ca2+-biosensorics analyses reveal that RBOHD phosphorylation by both kinases is essential for elicitor triggered systemic Ca2+ signalling and innate immunity manifestation. Notably, combined CIPK26/CPK5 action dramatically lowers the Ca2+ concentration threshold of RBOHD activation, and phosphorylation of RBOHD Ser343/347 provides a complementary cis-acting substrate-sensitisation/activation mechanism through determining its Ca2+ binding efficiency. These dual signalling sensitisation and actuation mechanisms maximize signal proliferation at minimized Ca2+ signal intensity to obviate interference of long distance and cellular Ca2+ signalling.
2024-11-28 | PXD038633 | JPOST Repository
Project description:<p>Healthy behavioral patterns could modulate organ functions to enhance the body’s immunity. However, whether exercise regulates antiviral innate immunity remains elusive. Here, we found that exercise promotes type-I IFN (IFN-I) production in the liver and enhances IFN-I immune activity of the body. Despite the possibility that many exercise-induced factors could regulate IFN-I production, we identified Gpld1 as a crucial molecule and the liver as the major organ to promote IFN-I production after exercise. Exercise largely loses the efficiency to induce IFN-I in Gpld1-/- mice. Further studies demonstrated that exercise-produced 3-hydroxybutanoic acid (3-HB) critically induces Gpld1 expression in the liver. Gpld1 blocks the PP2A-IRF3 interaction and therefore enhances IRF3 activation and IFN-I production, and improves the body’s antiviral ability. This study reveals that the exercise behavior improves antiviral innate immunity by linking the liver metabolism to systemic IFN-I activity, and uncovers an unknown function of liver cells in innate immunity.</p>
2024-04-24 | MTBLS7972 | MetaboLights
Project description:Leaf-to-leaf, systemic immune signaling known as systemic acquired resistance (SAR) is poorly understood in monocotyledonous plants. Here, we characterize systemic immunity in barley (Hordeum vulgare) triggered after primary leaf infection with either Pseudomonas syringae pathovar japonica (Psj) or Xanthomonas translucens pathovar cerealis (Xtc). Both pathogens induced resistance in systemic, uninfected leaves against a subsequent challenge infection with Xtc. In contrast to SAR in Arabidopsis thaliana, systemic immunity in barley was not associated with NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 or the local or systemic accumulation of salicylic acid (SA). Instead, we documented a moderate local but not systemic induction of abscisic acid (ABA) after infection of leaves with Psj. In contrast to SA or its functional analog benzothiadiazole, local applications of the jasmonic acid methyl ester or ABA triggered systemic immunity to Xtc. RNA-seq analysis of local and systemic transcript accumulation revealed unique gene expression changes in response to both Psj and Xtc and a clear separation of local from systemic responses. The systemic response appeared relatively modest and quantitative RT-PCR associated systemic immunity with the local and systemic induction of two WRKY and two ETHYLENE RESPONSIVE FACTOR-like transcription factors. Systemic immunity against Xtc was further associated with transcriptional changes after a secondary/systemic Xtc challenge infection; these changes were dependent on the primary treatment. Taken together, bacteria-induced systemic immunity in barley may be mediated in part by WRKY and ERF-like transcription factors possibly facilitating transcriptional reprogramming to potentiate immunity.
2014-11-24 | E-MTAB-3063 | biostudies-arrayexpress
Project description:Leaf-to-leaf, systemic immune signaling known as systemic acquired resistance (SAR) is poorly understood in monocotyledonous plants. Here, we characterize systemic immunity in barley (Hordeum vulgare) triggered after primary leaf infection with either Pseudomonas syringae pathovar japonica (Psj) or Xanthomonas translucens pathovar cerealis (Xtc). Both pathogens induced resistance in systemic, uninfected leaves against a subsequent challenge infection with Xtc. In contrast to SAR in Arabidopsis thaliana, systemic immunity in barley was not associated with NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 or the local or systemic accumulation of salicylic acid (SA). Instead, we documented a moderate local but not systemic induction of abscisic acid (ABA) after infection of leaves with Psj. In contrast to SA or its functional analog benzothiadiazole, local applications of the jasmonic acid methyl ester or ABA triggered systemic immunity to Xtc. RNA-seq analysis of local and systemic transcript accumulation revealed unique gene expression changes in response to both Psj and Xtc and a clear separation of local from systemic responses. The systemic response appeared relatively modest and quantitative RT-PCR associated systemic immunity with the local and systemic induction of two WRKY and two ETHYLENE RESPONSIVE FACTOR-like transcription factors. Systemic immunity against Xtc was further associated with transcriptional changes after a secondary/systemic Xtc challenge infection; these changes were dependent on the primary treatment. Taken together, bacteria-induced systemic immunity in barley may be mediated in part by WRKY and ERF-like transcription factors possibly facilitating transcriptional reprogramming to potentiate immunity.
2014-11-24 | E-MTAB-3056 | biostudies-arrayexpress
Project description:Barley Systemic Immunity: Dataset Local and Systemic
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