Journal article
Trained Immunity Confers Broad-Spectrum Protection Against Bacterial Infections.
- Ciarlo E Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Epalinges, Switzerland.
- Heinonen T Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Epalinges, Switzerland.
- Théroude C Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Epalinges, Switzerland.
- Asgari F Department of Biomedical Sciences, Humanitas University, Milan, Italy.
- Le Roy D Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Epalinges, Switzerland.
- Netea MG Radboud Center for Infectious Diseases, and Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
- Roger T Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Epalinges, Switzerland.
- 2020-01-01
Published in:
- The Journal of infectious diseases. - 2020
Listeria
innate immunity
infection
monocyte/macrophage
neutrophil
peritonitis
pneumonia
sepsis
stem cell
trained immunity
English
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.
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.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1093/infdis/jiz692
- PMID 31889191
- Persistent URL
- https://folia.unifr.ch/global/documents/145036
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