Document Type
Article
Publication Date
1-1-2014
Description
Upon priming with Candida albicans or with the fungal cell wall component β-glucan, monocytes respond with an increased cytokine production upon restimulation, a phenomenon termed "trained immunity." In contrast, the prestimulation of monocytes with lipopolysaccharide has long been known to induce tolerance. Because the vast majority of commensal microorganisms belong to bacterial or viral phyla, we sought to systematically investigate the functional reprogramming of monocytes induced by the stimulation of pattern recognition receptors (PRRs) with various bacterial or viral ligands. Monocytes were functionally programmed for either enhanced (training) or decreased (tolerance) cytokine production, depending on the type and concentration of ligand they encountered. The functional reprogramming of monocytes was also associated with cell shape, granulocity, and cell surface marker modifications. The training effect required p38- and Jun N-terminal protein kinase (JNK)-mediated mitogen-activated protein kinase (MAPK) signaling, with specific signaling patterns directing the functional fate of the cell. The long-term effects on the function of monocytes were mediated by epigenetic events, with both histone methylation and acetylation inhibitors blocking the training effects. In conclusion, our experiments identify the ability of monocytes to acquire adaptive characteristics after prior activation with a wide variety of ligands. Trained immunity and tolerance are two distinct and opposing functional programs induced by the specific microbial ligands engaging the monocytes.
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.
Citation Information
Ifrim, Daniela C.; Quintin, Jessica; Joosten, Leo A.B.; Jacobs, Cor; Jansen, Trees; Jacobs, Liesbeth; Gow, Neil A.R.; Williams, David L.; Van Der Meer, Jos W.M.; and Netea, Mihai G.. 2014. Trained Immunity or Tolerance: Opposing Functional Programs Induced in Human Monocytes After Engagement of Various Pattern Recognition Receptors. Clinical and Vaccine Immunology. Vol.21(4). 534-545. https://doi.org/10.1128/CVI.00688-13 PMID: 24521784 ISSN: 1556-6811
Copyright Statement
Copyright © 2014 Ifrim et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license.