title: Innate immune memory: Implications for host responses to damage-associated molecular patterns.
abstract: Cells of the innate immune system build immunological memory via epigenetic reprogramming after stimulations with microbial ligands. This functional readjustment allows for enhanced nonspecific inflammatory responses upon secondary challenges, a process termed "trained immunity." The epigenomic blueprint of trained monocytes has been recently reported, which revealed several important immunologic and metabolic mechanisms that underlie these changes. Interestingly, similar long-term reprogramming of cytokine production has also been described to be induced by endogenous damage-associated molecular patterns (DAMPs). Here, we present an overview of the novel data showing that endogenous alarm signals associated with tissue damage and sterile inflammation can induce trained immunity through epigenetic regulation of transcriptional programs. We describe new and old evidence of persistent effects of DAMPs in driving inflammation and enforce the concept that the influence of tissue-derived signals is critical in adjusting the magnitude and type of immune response built by the host. The better characterization of trained immunity for the persistence of inflammation induced by DAMPs would provide new possibilities for intervention in aging and autoinflammatory disorders.
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Medical Genetics, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Tania O
authors.initials: TO
authors.lastname: Crișan
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
mesh_terms: D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D051192:Receptors, Pattern Recognition / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D016207:Cytokines; D051192:Receptors, Pattern Recognition
keywords: Damage-associated molecular patterns ⋅ Epigenetics ⋅ Innate immune memory ⋅Trained immunity