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.
Highlights
Immunological studies on plants and invertebrates – both lacking adaptive immune responses – have suggested that these organisms can become increasingly resistant to reinfections, it was long believed that only B and T cells can confer immunological memory to their host [2–4]
The studies presented in this review clearly put the hematopoietic stem and progenitor cells (HSPCs) compartment at the foundation of the long-term effects exerted by trained immunity
Direct induction of trained immunity in HSPCs results in the production of a myeloid progeny with a trained phenotype directly inherited from their progenitors
Summary
The immune system of vertebrates has been binary classified into the innate and adaptive arms of immunity. The systemic administration of poly(I:C) – a strong inducer of type-I IFNs – recapitulated the negative impact on myelopoiesis observed in Mtb-infected animals, which was completely reverted in Ifnar1-/mice Taken together, these studies suggest that the balance between type-I and type-II IFN signaling by HSPCs plays a key role in the induction of a detrimental or protective innate immune memory in vivo. This was possibly the result of the initial expansion of a CD61+ subset of LT-HSCs in the aged mice, which were found to be more proliferative and intrinsically prone to a myeloid output [62] Taken together, these studies suggest that direct TLR ligation on HSPCs plays an important role in the terminal differentiation of the cells as well as the establishment of innate immune memory. Both direct TLR signaling and the indirect signaling autocrinally induced by the production of cytokines seem to be involved in this complex phenomenon
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