Details

Autor(en) / Beteiligte

• Ciarlo, Eleonora
• Heinonen, Tytti
• Théroude, Charlotte
• Asgari, Fatemeh
• Le Roy, Didier
• Netea, Mihai G
• Roger, Thierry

Titel

Trained Immunity Confers Broad-Spectrum Protection Against Bacterial Infections

Ist Teil von

• The Journal of infectious diseases, 2020-12, Vol.222 (11), p.1869-1881

Ort / Verlag

US: Oxford University Press

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract Background The innate immune system recalls a challenge to adapt to a secondary challenge, a phenomenon called trained immunity. Training involves cellular metabolic, epigenetic and functional reprogramming, but how broadly trained immunity protects from infections is unknown. For the first time, we addressed whether trained immunity provides protection in a large panel of preclinical models of infections. Methods Mice were trained and subjected to systemic infections, peritonitis, enteritis, and pneumonia induced by Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, Citrobacter rodentium, and Pseudomonas aeruginosa. Bacteria, cytokines, leukocytes, and hematopoietic precursors were quantified in blood, bone marrow, and organs. The role of monocytes/macrophages, granulocytes, and interleukin 1 signaling was investigated using depletion or blocking approaches. Results Induction of trained immunity protected mice in all preclinical models, including when training and infection were initiated in distant organs. Trained immunity increased bone marrow hematopoietic progenitors, blood Ly6Chigh inflammatory monocytes and granulocytes, and sustained blood antimicrobial responses. Monocytes/macrophages and interleukin 1 signaling were required to protect trained mice from listeriosis. Trained mice were efficiently protected from peritonitis and listeriosis for up to 5 weeks. Conclusions Trained immunity confers broad-spectrum protection against lethal bacterial infections. These observations support the development of trained immunity-based strategies to improve host defenses. We used preclinical models to demonstrate that trained immunity confers broad-spectrum protection against bacterial infections. Trained immunity increased myeloid progenitors and circulating inflammatory monocytes and neutrophils, and depletion or neutralization of monocytes/macrophages and interleukin 1 signaling impaired trained immunity-mediated protection.