Train the Trainer: Hematopoietic Stem Cell Control of Trained Immunity

Abstract

Recent evidence shows that innate immune cells, in addition to B and T cells, can retain immunological memory of their encounters and afford long-term resistance against infections in a process known as ‘trained immunity’. However, the duration of the unspecific protection observed in vivo is poorly compatible with the average lifespan of innate immune cells, suggesting the involvement of long-lived cells. Accordingly, recent studies demonstrate that hematopoietic stem and progenitor cells (HSPCs) lay at the foundation of trained immunity, retaining immunological memory of infections and giving rise to a “trained” myeloid progeny for a long time. In this review, we discuss the research demonstrating the involvement of HSPCs in the onset of long-lasting trained immunity. We highlight the roles of specific cytokines and Toll-like receptor ligands in influencing HSPC memory phenotypes and the molecular mechanisms underlying trained immunity HSPCs. Finally, we discuss the potential benefits and drawbacks of the long-lasting trained immune responses, and describe the challenges that the field is facing.

Enriched dietary saturated fatty acids induce trained immunity via ceramide production that enhances severity of endotoxemia and clearance of infection

“…Specifically, trained immunity is an innate immune memory response characterized by reprogramming of myeloid cells by a primary inflammatory stimulus, that then responds more robustly to secondary inflammatory challenge. Trained immunity has been shown to mediate cell sub-types within the HSC compartment that gives rise to “trained” myeloid progeny for weeks to years ( De Zuani and Frič, 2022 ). A previous study in Ldlr −/− mice has shown 4 weeks of WD feeding significantly enhances multipotent progenitors (MPPs) and granulocyte and monocyte precursors (GMPs) and skews development of GMPs toward a monocyte lineage that is primed to respond with a hyper-inflammatory response to LPS ( Christ et al, 2018 ).…”

Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent Mycobacterium tuberculosis

“…Interestingly, mitochondrial damage has been reported in monocytes of TB patients, which could render these cells more susceptible to cell death [ 27 ]. In consonance, M. tb infection in mice has been shown to induce a dysregulation in the mitochondrial membrane potential in myeloid progenitors, to induce an unanticipated immune evasion in bone marrow and to control the intrinsic antimicrobial capacity of innate immunity, a process suggested as innate immunity training in some infections [ 28 , 29 ].…”