Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell RNA sequencing reveals how myeloid cell reprogramming by commensal Prevotella enhances defense against Streptococcus pneumoniae lung infection

ABSTRACT: Streptococcus pneumoniae expresses a suite of virulence factors that modulate the innate immune response, delaying effective clearance. However, immune interactions with other bacteria influence this dynamic. Depletion of respiratory tract anaerobes including Prevotella is associated with increased mortality from pneumonia, an effect that can be replicated by pre-exposure to Prevotella melaninogenica in mice. Here, we demonstrate using single-cell RNA sequencing that P. melaninogenica shifts myeloid cell transcriptional profiles during pneumococcal infection from interferon-dominant to pro-phagocytic, correlating with increased S. pneumoniae phagocytosis and clearance from the lung. In neutrophils, improved antibacterial defense was dependent on TNF signaling through TNFR2. Prevotella-enhanced defense also required the recruitment of monocyte-derived macrophages, with selective enrichment of a Cxcl3+ population which differed from the C1qa+ population dominant during S. pneumoniae infection in unprimed mice. This work reveals an optimized innate immune defense program which may contribute to natural infection resistance mediated by respiratory tract commensal-host interactions.

ORGANISM(S): Mus musculus

PROVIDER: GSE313404 | GEO | 2026/06/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

CFTR mutation abrogates Prevotella regulation of epithelial cell defense against Staphylococcus aureus

Project description:Background: The oral anaerobe Prevotella melaninogenica is enriched in the lungs of people with cystic fibrosis (pwCF), yet its functional impact on respiratory tract homeostasis remains incompletely understood. Prior studies identified immune modulatory effects following lung exposure to Prevotella, but the relevance of these findings for CF infections is unknown. Methods: The impact of P. melaninogenica on infection with the CF pathogen Staphylococcus aureus was evaluated using a mouse lung infection model and human respiratory tract cystic fibrosis transmembrane conductance regulator (CFTR) mutant and isogenic wild-type (WT)-corrected CFBE41o- epithelial cells. RNA-sequencing was performed to compare Prevotella-induced signaling programs in WT-corrected versus CFTR mutant cells. Results: P. melaninogenica significantly reduced S. aureus lung infection, which was associated with elevated S. aureus killing by lung neutrophils and impaired S. aureus adherence to epithelial cells. Live or heat-killed Prevotella were sufficient to mediate these effects, which were dependent on the toll-like receptor TLR2. Prevotella impairment of S. aureus adherence also required CFTR function, as this effect was lost in CFTR mutant cells but restored by CFTR modulator therapy. RNA-sequencing identified several antibacterial defense pathways selectively upregulated by Prevotella in WT corrected epithelial cells, correlating with higher IL-8 and IL-6 cytokine production. Conclusions: P. melaninogenica enhanced neutrophil and epithelial defense against S. aureus, but these benefits were lost with CFTR dysfunction. CFTR modulator therapy rescued Prevotella responsiveness in respiratory epithelial cells, highlighting the potential for synergistic effects of host-microbiome interactions and CFTR targeted therapies.

2025-12-09 | GSE305398 | GEO

Epithelial cells maintain memory of prior infection with Streptococcus pneumoniae through di-methylation of histone H3 [ChIPseq]

Project description:Epithelial cells are the first point of contact for bacteria entering the respiratory tract. Streptococcus pneumoniae is an obligatory human pathobiont of the nasal mucosa, carried asymptomatically but also the cause of severe pneumoniae. The role of the epithelium in maintaining homeostatic interactions or mounting an inflammatory response to invasive S. pneumoniae is currently poorly understood. However, studies have shown that chromatin modifications, at the histone level, induced by bacterial pathogens interfere with the host transcriptional program and promote infection. In this study, we demonstrate that S. pneumoniae actively induces di-methylation of histone H3 on lysine 4 (H3K4me2), which persists for at least 9 days upon clearance of bacteria with antibiotics. We show that infection establishes a unique epigenetic program affecting the transcriptional response of epithelial cells, rendering them more permissive upon secondary infection. Our results establish H3K4me2 as a unique modification induced by infection, distinct from H3K4me3, which localizes to enhancer regions genome-wide. Therefore, this study reveals evidence that bacterial infection leaves a memory in epithelial cells after bacterial clearance, in an epigenomic mark, thereby altering cellular responses for subsequent infections.

2024-05-17 | GSE230141 | GEO

Epithelial cells maintain memory of prior infection with Streptococcus pneumoniae through di-methylation of histone H3 [Affymetrix]

2024-05-17 | GSE230138 | GEO

Prevotella melaninogenica

Project description:Prevotella melaninogenica overview

| PRJNA37359 | ENA

Trancriptome profiling of murine lung after pneumococcal respiratory infection, antibiotic administation, and treatment with immunostimulants

Project description:The study aimed at defining the transcriptional responses of the respiratory tract after respiratory infection with Streptococcus pneumoniae, treatment with antibiotic and administration of immunostimulatory molecules. For this purpose, mice were infected by intranasal route with S. pneumoniae. After 12h, animals were treated by orogastric administration of amoxicillin and either intraperitoneal injection of monophosphoryl lipid A or intranasal instillation of flagellin FliC∆174-400. Whole lungs were then sampled at selected times for microarray analyses.

2021-07-29 | GSE118860 | GEO

Comparative DDA and DIA-PASEF proteomics profiling of cross-kingdom macrophage infection reveals new mechanisms driving pathogen virulence

Project description:Opportunistic infections of the respiratory tract often succeed under a weakened immune response caused by an underlying illness or hospitalization. The human fungal pathogen, Cryptococcus neoformans, and the bacterial pathogen, Klebsiella pneumoniae, are both well-characterized microbes that cause severe infections within immunocompromised individuals. In this study, we simulate a concentration-dependent pulmonary coinfection of a bacterial and fungal pathogen, and profile the proteomic changes by DDA vs. DIA. Dual perspective profiling provides new insights into host defense regulation of infection and pathogenic mechanisms of invasion.

2024-08-13 | PXD054527 | Pride

Transcriptome sequencing of primary human oral keratinocytes co-cultured with Prevotella melaninogenica

Project description:Oral lichen planus (OLP) is a common oral mucosal disease, of which the etiology and pathogenesis are still unclear. Microorganisms may play an essential role in the pathogenesis of OLP. Previous studies of our group found that the composition ratio of Prevotella melaninogenica (Pm) on the buccal mucosa surface of OLP patients increased significantly. In addition, Pm could invade the epithelium of OLP. As the first physical defense of the oral mucosa, oral keratinocytes may interact directly with Pm in OLP. Therefore, this study aimed to explore the impact of Pm on primary human oral keratinocytes' transcriptome.

2022-12-14 | GSE220609 | GEO

Bovine Respiratory Disease Complex

Project description:Bovine respiratory epithelial cells have different susceptibility to bovine respiratory syncytial virus infection. The cells derived from the lower respiratory tract were significantly more susceptible to the virus than those derived from the upper respiratory tract. Pre-infection with virus of lower respiratory tract with increased adherence of P. multocida; this was not the case for upper tract. However, the molecular mechanisms of enhanced bacterial adherence are not completely understood. To investigate whether virus infection regulates the cellular adherence receptor on bovine trachea-, bronchus- and lung-epithelial cells, we performed proteomic analyses.

2020-07-28 | PXD019509 | JPOST Repository

Project description:Lower respiratory tract infection caused by Klebsiella pneumoniae

| PRJNA1113824 | ENA

Microbiome Modulation Uncouples Efficacy and Toxicity Induced by Programmed Death-1/Programmed Death-Ligand1 Blockade in multiple myeloma

Project description:Intestinal microbiota and gut-born T helper-17 (Th17) lymphocytes may act as drivers of smoldering multiple myeloma (SMM) to MM evolution. We demonstrate here that administering the human commensal Prevotella melaninogenica to transgenic Vk*MYC mice affected by Early-MM, mimicking human SMM, significantly delayed evolution to full-blown MM. Mechanistically, P. melaninogenica increased the production of short-chain fatty acids (SCFAs), preventing skew of dendritic cells towards a pro-Th17 phenotype and accumulation of Th17 cells in the bone marrow of treated mice. P. melaninogenica or butyrate synergized with anti-PD-L1 antibodies by restraining Th17 cell expansion while unleashing immune checkpoint blockade (ICB)-induced effector CD8+ T cells. P. melaninogenica also attenuated IL-17-mediated skin lesions that mimicked ICB-induced immune-related adverse events. Thus, modulation of the gut microbiota or SCFAs administration with or without ICB might represent treatment options for patients affected by plasma cell dyscrasias and other hematologic or solid tumors where IL-17 acts as driving force.

2025-10-03 | GSE306088 | 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