Trained immunity confers broad-spectrum protection against bacterial infections

Trained immunity confers broad-spectrum protection against bacterial infections:

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 IL-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 Ly6C^high inflammatory monocytes and granulocytes, and sustained blood antimicrobial responses. Monocytes/macrophages and IL-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.