Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia

ABSTRACT: Novel therapeutic approaches for addressing pneumonia caused by Streptococcus pneumoniae, which exhibit resistance to standard-of-care antibiotics are greatly needed. One viable approach involves precisely stimulating innate immune defenses within the lungs. Using murine models of pneumococcal pneumonia, prior studies demonstrated that intranasal administration of the Toll-like receptor 5 agonist, flagellin, results in a 100-fold decrease in lung infection compared to sole antibiotic therapy, when used as an adjunct treatment to the antibiotic. To promote the transfer of this immunotherapy to clinics and mitigate unwanted systemic inflammation, this project assessed whether the direct delivery of flagellin to the airways through nebulization stimulates respiratory defenses against bacterial infection. Similarly to intranasal administration, nebulized flagellin induced a transient activation of lung innate immunity. In contrast, inhalation by nebulization resulted in an attenuated activation of systemic immune responses. We conclude that flagellin aerosol therapy represents a secure and promising approach in addressing bacterial pneumonia within the context of antimicrobial resistance.

ORGANISM(S): Mus musculus

PROVIDER: GSE252037 | GEO | 2024/10/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia

Project description:Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia

| PRJNA1057163 | ENA

Amoxicillin treatment of pneumococcal pneumonia impacts bone marrow neutrophil maturation and function.

Project description:Pneumonia caused by Streptococcus pneumoniae is a leading cause of death worldwide, and bacterial resistance to antimicrobial drugs has become a major issue. A growing body of evidence indicates that the successful treatment of bacterial infections results from synergy between antibiotic-mediated direct antibacterial activity and the host’s immune defenses. However, the mechanisms underlying the protective immune responses induced by amoxicillin (a β-lactam antibiotic used as the first-line treatment of S. pneumoniae infections) have not been characterized. A better understanding of amoxicillin’s effects on host-pathogen interactions might facilitate the development of other treatment options. Given the crucial role of neutrophils in the control of S. pneumoniae infections, we decided to investigate amoxicillin’s impact on neutrophil development in a mouse model of pneumococcal superinfection. Although a single therapeutic dose of amoxicillin prevented local and systemic inflammatory responses, it did not impair the emergency granulopoiesis triggered in the bone marrow by S. pneumoniae. Importantly, treatment of pneumonia with amoxicillin was associated with a greater mature neutrophil count in the bone marrow; these neutrophils had specific transcriptomic and proteomic profiles. Furthermore, amoxicillin-conditioned, mature neutrophils in the bone marrow had a less activated phenotype and might be rapidly mobilized in peripheral tissues in response to systemic inflammation. Thus, by revealing a novel effect of amoxicillin on the development and functions of bone marrow neutrophils during Streptococcus pneumoniae pneumonia, our findings provide new insights into the impact of amoxicillin treatment on host immune responses.

2023-10-09 | PXD042496 | Pride

Lung conventional dendritic cells promote mucosal adjuvant activity of flagellin

Project description:The activity of the potent nasal adjuvant flagellin depends on initial activation of airway epithelilal cells. This study aims at investigating the immune cells involved in the antigen presentation within the respiratory tract. First, microarrays characterized that activation/recruitment of immune cells was the main signature of flagellin activation in lung. Neutrophils and classical monocytes were strongly recruited into the lungs and take up antigen upon nasal administration of flagellin. In contrast, the numbers of lung CD11b+ or CD103+ DC and alveolar macrophages were not enhanced although these cells were very efficient in antigen uptake. Our experiments showed that CD11b+ DC but not monocytes, PMN, CD103+ DC are not essential for the adjuvant effect. Flagellin signaling enhanced the functional activation of lung CD11b+ conventional DC and their migration to the lymph nodes. Using Cd11c-DTR mice, CD11b+ DC from lymph nodes were identified as the major stimulators of CD4 T cell activation. Finally, the migration and maturation of mucosal DC was independent of direct signaling, highlighting the contribution of epithelial factors in the mucosal adjuvant effect of flagellin. In conclusion, these data demonstrate that adjuvant activity can be dissociated from inflammatory cell recruitment an open new perpectives for improvement of vaccines. Female C57BL/6J (6 weeks old) mice were immunized with the TLR5 agonist Flagellin (1Î¼g diluted in PBS) by intranasal (i.n.) administration. Blood samples of four time points post immunization were taken at 2h, 4h, 18h and 48h. Microarray experiments were performed as single-color hybridizations.

2014-01-01 | E-GEOD-46421 | biostudies-arrayexpress

Airway neutrophils actively enhance the therapeutic efficacy of flagellin in treating pneumococcal pneumonia

Project description:Host-directed therapy, using nasal administration of the Toll-like receptor 5 agonist flagellin in combination with antibiotics, has demonstrated effectiveness against pneumococcal pneumonia. In this study, we investigated the immune mechanisms underlying the protective effects. Transcriptomic analysis of lung tissue during infection revealed that flagellin not only enhanced pathways associated with myeloid cell infiltration into the airways and antimicrobial functions, but also promoted the early and transient mobilization of neutrophils and inflammatory monocytes. Neutrophils were identified as crucial for the protective effects of flagellin. The adjunct activity of flagellin correlated with the increased recruitment of neutrophils into airways, their localization at the periphery of bronchi, alveoli, and lung vessels, along with alterations in phagocytic activity. Lastly, single-cell analysis highlighted that the treatment stimulated the recruitment of specific neutrophil subsets capable of enhancing antibacterial effectiveness. In conclusion, this study highlights neutrophils as an appealing target for host-directed therapy in infection.

2024-11-14 | GSE269163 | GEO

Cytosolic flagellin receptor NLRC4 protects mice against mucosal and systemic challenges

2012-01-01 | GSE34492 | GEO

Cytosolic flagellin receptor NLRC4 protects mice against mucosal and systemic challenges

Project description:Bacterial flagellin is a dominant innate immune activator of the intestine. Therefore, we examined the role of the intracellular flagellin receptor, NLRC4, in protecting the gut and/or driving inflammation. In accord with NLRC4 acting via transcription-independent pathways, loss of NLRC4 did not reduce the rapid robust changes in intestinal gene expression induced by flagellin administration. Loss of NLRC4 did not alter basal intestinal homeostasis nor predispose mice to development of colitis upon administration of an anti-IL-10R monoclonal antibody. However, in response to epithelial injury induced by dextran sulfate sodium (DSS), loss of NLRC4 resulted in more severe disease indicating a role for NLRC4 in protecting the gut. Moreover, loss of NLRC4 resulted in increased mortality in response to flagellate, but not aflagellate Salmonella infection. Thus, despite not being involved in rapid intestinal gene remodeling upon detection of flagellin, NLRC4-mediated inflammasome activation protects mice from mucosal and systemic challenges Flagellin (FliC) from WT Salmonella enterica serovar Typhimurium (SL3201, fljB–) was purified through sequential cation and anion-exchange chromatography and purity was verified as previously described 4. WT, T5KO, N4KO and T5/N4-DKO mice (n=6) were given either 0.2 mL PBS or flagellin (10μg/mouse in 0.2 mL PBS) intraperitoneally. After 1h, mice were euthanized and colon was taken and stored in RNAlater (Invitrogen) for 1 day. Total mRNA was isolated from colonic tissues using TRIzol (Invitrogen) and purified using the RNeasy® Plus Mini kit (Qiagen) according to the manufacturer’s instructions

2012-01-01 | E-GEOD-34492 | biostudies-arrayexpress

Genome-wide analysis of whole-lung and alveolar macrophages before and after gut microbiome depletion

Project description:Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota has emerged as a key defense system by local support of mucosal immunity as well as proposed modulatory effects on systemic immunity. We here investigated the transcriptomes of whole-lungs and alveolar macrophages between untreated and antibiotic treated mice.

2016-12-09 | GSE53174 | GEO

Dysregulation of Streptococcus pneumoniae zinc homeostasis breaks ampicillin resistance in a pneumonia infection model

Project description:This study reports on the co-administration of a zinc ionophore (PBT-2) and ampicillin to break antibiotic resistance of Streptococcus pneumoniae in a murine pneumonia model. The molecular mechanism for this heightened antimicrobial activity was identified through transcriptomic and metabolomic analyses of a wild type strain and a zinc efflux mutant to identify cellular targets of zinc intoxication. This revealed that zinc intoxication induces numerous cellular disruptions, which when combined with frontline antibiotics, can break antibiotic resistance and potentially preclude further resistance from emerging.

2022-02-01 | GSE159901 | GEO

Fungal Dysbiosis in Post-Influenza MRSA Infection

Project description:A leading cause of morbidity and mortality during influenza infection is the development of a secondary bacterial pneumonia, which is appropriately treated with antibiotics. In the absence of a bacterial superinfection, prescribing antibiotics is not indicated but has nevertheless become a common clinical practice for those presenting with a respiratory viral illness. We found that antibiotic use during an antecedent influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistantStaphylococcus aureus(MRSA). The antibiotics perturbed the gut microbiome causing a fungal dysbiosis that drives an increase in lung eosinophils. We also demonstrate eosinophils, through the release of major basic protein, impair macrophage ability to clear MRSA. Moreover, we provide clinical evidence that eosinophils positively correlate with antibiotic use and worsened outcomes in patients hospitalized for viral infections. Altogether, our work establishes a counterproductive effect of antibiotic treatment during influenza infection that have negative immunologic consequences in the lungs thereby increasing the risk of developing a secondary bacterial infection.

2024-08-21 | GSE243542 | 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