Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lung microbiota coordinates alveolar macrophage and γδ T cell activation against Klebsiella pneumoniae via SCFA-FFAR2 axis

ABSTRACT: Here, we show that intratracheal vancomycin-induced lung dysbiosis renders mice more susceptible to K. pneumoniae and dampens immune responses to LPS, characterized by reduced IL-17A production and impaired activation of IL-17A+ γδ T cells in the lung. This effect is dependent on decreased IL-1β secretion from alveolar macrophages (AMs), accompanied by restrained NF-κB and GPR signaling. Additionally, lung dysbiosis reduces microbiota-derived SCFAs in the lung, while FFAR2, their major receptor, is predominantly expressed on AMs. Furthermore, acetate activation of FFAR2 on AMs enhances NF-κB phosphorylation, inflammasome activation, and IL-1β production, promoting IL-17A+ γδ T cell activation. Moreover, acetate supplementation rescued lung dysbiosis-suppressed immune responses and host defense in a FFAR2-dependent manner on AMs. In conclusion, lung microbiota-derived SCFAs coordinate the activation of AMs and γδ T cells through FFAR2, suggesting that lung dysbiosis compromises the protective role of commensal bacteria in modulating innate immune network against K. pneumoniae infections.

ORGANISM(S): Mus musculus

PROVIDER: GSE309138 | GEO | 2026/04/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Vγ6+ γδ T cells play a critical role in protection against infection by Escherichia coli

Project description:γδ T cells producing interleukin 17A (IL-17A), which are mainly Vγ4 and Vγ6 subsets, are involved in protection against infection by extracellular bacteria. Using a new Vγ6-specific monoclonal antibody (mAb) (1C10-1F7) which we recently developed, we found that IL-17A+ Vγ6+ γδ T cells increased predominantly in the peritoneal cavity compared with IL-17A+ Vγ4+ γδ T cells during intraperitoneal Escherichia coli infection. The number of IL-17A+ Vγ6+ γδ T cells, which rapidly became CD69+ from CD69-, peaked at 12 h after infection. In vivo treatment with 1C10-1F7 mAb significantly inhibited the accumulation of neutrophils and hampered the resolution of E. coli infection. These results suggest that rapid activation of IL-17A+ Vγ6+ γδ T cells contributed to host defence against E. coli infection.

2020-02-28 | GSE144617 | GEO

γδ T cells orchestrate the induction of protective type 2 immunity in neonatal influenza infection

Project description:Influenza infection causes high rates of hospitalization and mortality in infants. γδ T cells are critical for immune responses against pathogens as regulators and effectors, especially in infants, and yet the roles of neonatal γδ T cells in influenza remain to be investigated. Here we report that γδ T cells were protective against mortality associated with neonatal influenza infection. Infection induced the accumulation and activation of γδ T cells, which transiently expressed IL-17a to enhance early IL-33 production by lung epithelial cells via STAT3 phosphorylation. Subsequently, this led to type 2 immune responses with elicited infiltration of ILC2s and Tregs resulting in increased amphiregulin secretion and tissue repair. Loss of γδ T cells did not alter viral clearance or IFN-γ production. Thus, our results identify a specific requirement for γδ T cells in influenza-infected neonates by initiating type 2 immune responses, mediating tissue homeostasis, and promoting lung integrity.

2018-06-20 | GSE99683 | GEO

Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma development

Project description:Dysbiosis, or changes within the microbiome, is a common feature of solid tumors, however whether this dysbiosis directly contributes to tumor development is largely unknown. We previously characterized the lung cancer microbiome and identified the Gram-negative Acidovorax temperans as enriched in tumors and associated with smoking status and TP53 mutations. To determine if A. temperans exposure could contribute to the development of lung cancer, we investigated its effect in an animal model of lung adenocarcinoma driven by mutant Kras and Tp53 alleles. This revealed A. temperans exposure accelerates tumor development and burden through infiltration of proinflammatory cells in the lungs. Neutrophils exposed to A. temperans displayed a mature, pro-tumorigenic phenotype with increased cytokine signaling, with a global shift away from IL-1β signaling. Neutrophil to monocyte and macrophage signaling promoted maturation of the latter cell types which upregulated MHC II to activate CD4+ T cells. Activated T cells were then polarized to an IL-17A+ phenotype detectable in CD4+ and γδ populations. Furthermore, T17 cells shared a common gene expression profile predictive of poor survival in human LUAD cases. These data indicate a clear role for microbiota-induced inflammation as a key mechanism in the development of lung cancer, demonstrating that dysbiosis contributes to tumor growth.

2022-07-07 | GSE207477 | GEO

TLR2 in γδ T cells is required for metabolic support of IL-17A ocular mucosal immune response to a commensal bacterium [ATAC-seq]

Project description:The ocular surface is colonized by commensal microbiota, which tune the local mucosal immune response. However, the mechanisms underlying the induction of an IL-17 response by γδ T cells in response to ocular commensal bacteria, particularly Corynebacterium mastitidis (C. mast), have not been fully investigated. Here, we demonstrated that intrinsic TLR2 activation in γδ T cells by commensal microbiota is required for their IL-17A production and fatty acid oxidation. We also identified IκBζ, a transcription factor whose expression is upregulated by TLR2 signaling, as a key regulator to enhance the expression of genes responsible for IL-17A production and FAO program. This study highlights the role of TLR2-mediated transcriptional regulation in targeting effector cytokines and metabolic programs to support IL-17A responses to commensal bacteria.

2024-05-15 | GSE236383 | GEO

TLR2 in γδ T cells is required for metabolic support of IL-17A ocular mucosal immune response to a commensal bacterium [RNA-seq]

2024-05-15 | GSE236386 | GEO

Lung microbiota coordinates alveolar macrophage and γδ T cell activation against Klebsiella pneumoniae via SCFA-FFAR2 axis

Project description:Lung microbiota coordinates alveolar macrophage and γδ T cell activation against Klebsiella pneumoniae via SCFA-FFAR2 axis

| PRJNA1334207 | ENA

Neutrophils negatively regulate IL-17 producing γδ T cells under physiological conditions

Project description:In addition to serving as the primary effector cells against infections, neutrophils have been implicated in the regulation of both innate and adaptive immunity. In this study, we employed neutropenic mice to investigate the role of neutrophils in the regulation of the immune system under physiological conditions. Unexpectedly, we observed an accumulation of γδ T cells in the cervical lymph nodes of neutropenic mice. Transcriptomic analysis revealed that these accumulated γδ T cells exhibited unique expression profiles of cell surface molecules and genes involved in defense responses. Further characterization indicated that the accumulated γδ T cells were IL-17 producing CD44+CD62L−CD27− memory cells. Additionally, in vitro experiments demonstrated that neutrophils could inhibit the function of IL-17A producing γδ T cells by inducing cell death in these activated cells. Given that IL-17A is a critical cytokine for the recruitment of neutrophils to peripheral tissues, our study suggests that the crosstalk between neutrophils and IL-17A producing γδ T cells is a crucial mechanism for maintaining immune homeostasis under physiological conditions

2025-04-09 | GSE272418 | GEO

Sepsis-induced acute lung injury is exacerbated by pulmonary Wnt signaling-dependent migration of small intestinal memory γδT17 cells to the lung

Project description:Sepsis, a worldwide health crisis, is notorious for its high mortality rate, often attributed to the development of acute lung injury. In this context, the lung, being particularly vulnerable to septic damage, emerge as a primary battleground. The possible roles of the gut-lung axis mediated by the gut microbiota and its metabolic products in the context of acute lung injury have been documented. However, the direct migration of intestinal immune cells to the lung as a mediator of acute lung injury remains unclear. Our study unveiled a process where cecal ligation and puncture-induced sepsis prompted a migration of γδ T cells from the small intestine to the lung, subsequently triggering an overwhelming inflammatory response dominated by IL-17A. Small intestinal memory γδT17 cells (CD44+ IL-7Rhigh CD8low Ly6C–) were the major subtype of γδ T cells that migrated from the small intestine to the lung and aggravated acute lung injury. Moreover, the activation of the Wnt signaling in the alveolar macrophages during sepsis was identified as a driving factor for the subsequent CCL1 upregulation, which prompted the migration of small intestinal memory γδT17 cells to the lung. S-Ketamine (S-KT) treatment demonstrated a notable capacity to alleviate acute lung injury through dampening pulmonary Wnt/β-catenin signaling-mediated migration of small intestinal γδT17 cells to the lung. Our findings highlight the significant contribution of the direct migration of immune cells from the small intestine to the lung in sepsis-induced acute lung injury, and clrify the pathological significance of the localized elevation of IL-17A in the lung.

2024-04-24 | PXD051763 |

Lamina propria Interleukin 17 A aggravates natural killer T cells activation in autoimmune hepatitis

Project description:Autoimmune hepatitis is an interface hepatitis characterized by the progressive destruction of the liver parenchyma, the cause of which is still obscure. Interleukin (IL)-17A is a major driver of autoimmunity, which can be produced by innate immune cells against several intracellular pathogens. Here, we investigated the involvement of IL-17A in a mice model of immune-mediated hepatitis with the intestine exposed to Salmonella typhimurium. Our results showed more severe Concanavalin (Con) A-induced liver injury and gut microbiome dysbiosis when the mice were treated with a gavage of S. typhimurium. Then the Natural Killer (NK) T cells were over-activated by the accumulated IL-17A in the liver in the Con A and S. typhimurium administration group. IL-17A could activate NKT cells by inducing CD178 expression via IL-4/STAT6 signaling. Furthermore, via the portal tract, the laminae propria mucosal-associated invariant T (MAIT) cell-derived IL-17A could be the original driver of NKT cells’ over-activation in intragastric administration of S. typhimurium and Con A injection. In IL-17A deficient mice, Con A-induced liver injury and NKT cells activation was alleviated. However, when AAV-sh-mIL-17a was used to specifically knock down IL-17A in liver, it seemed that hepatic IL-17a knock down did not significantly influence the liver injury. Our results suggested that, under Con A-induction, laminae propria MAIT-derived IL-17A activated hepatic NKT, and this axis could be a therapeutic target in autoimmune liver disease.

2023-03-01 | GSE199311 | GEO

Reduced TCRγδ signal strength engages phosphatidylinositol 3-kinase (PI3K) to drive thymic development of IL-17A-secreting γδ T cells

Project description:Reduced TCRγδ signal strength manifest by constrained Syk activity engages PI3K to maintain expression of key master regulators of the IL-17 program; RORγt and c-Maf, and drive thymic development of IL-17A-secreting γδ T cells (γδ17 cells). Notably, inhibition of PI3K not only abrogates γδ17 cell development, but also permits γδ progenitors to adopt a type-I interferon gene expression signature that identifies a novel CD8(+)Sca-1(+) γδ T cell subset.

2021-07-05 | GSE167943 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data