DAMPs and Innate Immune Training.

Elisa Jentho,Sebastian Weis

doi:10.3389/fimmu.2021.699563

Abstract

The ability to remember a previous encounter with pathogens was long thought to be a key feature of the adaptive immune system enabling the host to mount a faster, more specific and more effective immune response upon the reencounter, reducing the severity of infectious diseases. Over the last 15 years, an increasing amount of evidence has accumulated showing that the innate immune system also has features of a memory. In contrast to the memory of adaptive immunity, innate immune memory is mediated by restructuration of the active chromatin landscape and imprinted by persisting adaptations of myelopoiesis. While originally described to occur in response to pathogen-associated molecular patterns, recent data indicate that host-derived damage-associated molecular patterns, i.e. alarmins, can also induce an innate immune memory. Potentially this is mediated by the same pattern recognition receptors and downstream signaling transduction pathways responsible for pathogen-associated innate immune training. Here, we summarize the available experimental data underlying innate immune memory in response to damage-associated molecular patterns. Further, we expound that trained immunity is a general component of innate immunity and outline several open questions for the rising field of pathogen-independent trained immunity.

Highlights

Monocytes and macrophages (Mj) are professional phagocytotic cells [1], a feature first described by Elie Metchnikoff almost 150 years ago [2]
Binding of pathogen-associated molecular patterns (PAMP) and danger-associated molecular pattern (DAMP) by pattern recognition receptors (PRRs) triggers distinct signaling transduction pathways which elicit the expression of immunomodulatory molecules, e.g. cytokines, indispensable for an appropriate immune reaction against an exogenous or endogenous threat
trained immunity (TRIM) can be induced by different classes of PRRs, as illustrated by b-glucan, which binds to the C-type lectin receptor Dectin-1 activating the noncanonical Raf-1 pathway signaling [12]

Summary

Introduction

Monocytes and macrophages (Mj) are professional phagocytotic cells [1], a feature first described by Elie Metchnikoff almost 150 years ago [2]. Subsequent work by other groups revealed that the fungal cell wall component b-1,3-D-glucan and other inflammatory stimuli can induce specific and persistent modifications of histone acetylation and methylation, underlying a long-term modulation of the innate immune response (Figure 1) [9, 11]. This raises the possibility that training, and tolerance are not unrelated phenomena but rather dependent on the re-writing of gene activation and repression programs via specific stimuli-induced signaling pathways to specify the reaction pattern of the innate immune cells.

Results

Conclusion