Dataset Information

?-Glucan-Induced Trained Immunity in Dogs.

ABSTRACT: Several observations in the world of comparative immunology in plants, insects, fish and eventually mammals lead to the discovery of trained immunity in the early 2010's. The first demonstrations provided evidence that innate immune cells were capable of developing memory after a first encounter with some pathogens. Trained immunity in mammals was initially described in monocytes with the Bacille Calmette-Guerin vaccine (BCG) or prototypical agonists like ?-glucans. This phenomenon relies on epigenetic and metabolic modifications leading to an enhanced secretion of inflammatory cytokines when the host encounters homologous or heterologous pathogens. The objective of our research was to investigate the trained immunity, well-described in mouse and human, in other species of veterinary importance. For this purpose, we adapted an in vitro model of trained innate immunity in dogs. Blood enriched monocytes were stimulated with ?-glucans and we confirmed that it induced an increased production of pro-inflammatory and anti-microbial compounds in response to bacterial stimuli. These results constitute the first demonstration of trained immunity in dogs and confirm its signatures in other mammalian species, with an implication of cellular mechanisms similar to those described in mice and humans regarding cellular epigenetics and metabolic regulations.

SUBMITTER: Paris S

PROVIDER: S-EPMC7581789 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

β-Glucan-Induced Trained Immunity in Dogs.

Paris Simon S Chapat Ludivine L Pasin Marion M Lambiel Manon M Sharrock Thomas E TE Shukla Rishabh R Sigoillot-Claude Cecile C Bonnet Jeanne-Marie JM Poulet Hervé H Freyburger Ludovic L De Luca Karelle K

Frontiers in immunology 20201009

Several observations in the world of comparative immunology in plants, insects, fish and eventually mammals lead to the discovery of trained immunity in the early 2010's. The first demonstrations provided evidence that innate immune cells were capable of developing memory after a first encounter with some pathogens. Trained immunity in mammals was initially described in monocytes with the Bacille Calmette-Guerin vaccine (BCG) or prototypical agonists like β-glucans. This phenomenon relies on epi ...[more]

PMID: 33162983

Similar Datasets

Project description:Background: Innate immune memory, also termed "trained immunity", is thought to protect against experimental models of infection, including sepsis. Trained immunity via reprogramming monocytes/macrophages has been reported to result in enhanced inflammatory status and antimicrobial activity against infection in sepsis. However, a safe and efficient way to induce trained immunity remains unclear. Methods: β-glucan is a prototypical agonist for inducing trained immunity. Ferumoxytol, superparamagnetic iron oxide (SPIO) with low cytotoxicity, has been approved by FDA for clinical use. We synthesized novel nanoparticles BSNPs by coupling β-glucan with SPIO. BSNPs were further conjugated with fluorescein for quantitative analysis and trace detection of β-glucan on BSNPs. Inflammatory cytokine levels were measured by ELISA and qRT-PCR, and the phagocytosis of macrophages was detected by flow cytometry and confocal microscopy. The therapeutic effect of BSNPs was evaluated on the well-established sepsis mouse model induced by both clinical Escherichia coli (E. coli) and cecal ligation and puncture (CLP). Results: BSNPs were synthesized successfully with a 3:20 mass ratio of β-glucan and SPIO on BSNPs, which were mainly internalized by macrophages and accumulated in the lungs and livers of mice. BSNPs effectively reprogrammed macrophages to enhance the production of trained immunity markers and phagocytosis toward bacteria. BSNP-induced trained immunity protected mice against sepsis caused by E. coli and CLP and also against secondary infection. We found that BSNP treatment elevated Akt, S6, and 4EBP phosphorylation, while mTOR inhibitors decreased the trained immunity markers and phagocytosis enhanced by BSNPs. Furthermore, the PCR Array analysis revealed Igf1, Sesn1, Vegfa, and Rps6ka5 as possible key regulators of mTOR signaling during trained immunity. BSNP-induced trained immunity mainly regulated cellular signal transduction, protein modification, and cell cycle by modulating ATP binding and the kinase activity. Our results indicated that BSNPs induced trained immunity in an mTOR-dependent manner. Conclusion: Our data highlight that the trained immunity of macrophages is an effective strategy against sepsis and suggest that BSNPs are a powerful tool for inducing trained immunity to prevent and treat sepsis and secondary infections.

Dataset Information

?-Glucan-Induced Trained Immunity in Dogs.

Publications

β-Glucan-Induced Trained Immunity in Dogs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets