Danger signals – damaged-self recognition across the tree of life

Abstract

Multicellular organisms suffer injury and serve as hosts for microorganisms. Therefore, they require mechanisms to detect injury and to distinguish the self from the non-self and the harmless non-self (microbial mutualists and commensals) from the detrimental non-self (pathogens). Danger signals are “damage-associated molecular patterns” (DAMPs) that are released from the disrupted host tissue or exposed on stressed cells. Seemingly ubiquitous DAMPs are extracellular ATP or extracellular DNA, fragmented cell walls or extracellular matrices, and many other types of delocalized molecules and fragments of macromolecules that are released when pre-existing precursors come into contact with enzymes from which they are separated in the intact cell. Any kind of these DAMPs enable damaged-self recognition, inform the host on tissue disruption, initiate processes aimed at restoring homeostasis, such as sealing the wound, and prepare the adjacent tissues for the perception of invaders. In mammals, antigen-processing and -presenting cells such as dendritic cells mature to immunostimulatory cells after the perception of DAMPs, prime naïve T-cells and elicit a specific adaptive T-/B-cell immune response. We discuss molecules that serve as DAMPs in multiple organisms and their perception by pattern recognition receptors (PRRs). Ca2+-fluxes, membrane depolarization, the liberation of reactive oxygen species and mitogen-activated protein kinase (MAPK) signaling cascades are the ubiquitous molecular mechanisms that act downstream of the PRRs in organisms across the tree of life. Damaged-self recognition contains both homologous and analogous elements and is likely to have evolved in all eukaryotic kingdoms, because all organisms found the same solutions for the same problem: damage must be recognized without depending on enemy-derived molecules and responses to the non-self must be directed specifically against detrimental invaders.

NAD Acts as an Integral Regulator of Multiple Defense Layers

“…ROS bursts contribute to basal defense responses after the perception of pathogen-associated molecular patterns (PAMPs), which are conserved molecules for a whole class of microbes, or via damage-associated molecular patterns (DAMPs), which are signals of cell disintegration (Heil and Land, 2014;Macho and Zipfel, 2014). Although some evidence indicates that exogenous NAD could act as a DAMP by leaking from an extracellular compartment and then stimulating immune responses (Zhang and Mou, 2009), this scenario awaits further investigation to determine how NAD intervenes in DAMP-triggered immunity.…”

A comparison of plants and animals in their responses to risk of consumption

“…In these experiments, plants responded most strongly to cues from their own tissues or those of closely related individuals. Cell wall fragments, extracellular DNA, and extracellular ATP are generalized cues of physical damage that elicit responses in both plants and animals [16 ]. Crickets sense speed of predator [73] Glandular trichomes…”

Key mechanisms involved in ionizing radiation-induced systemic effects. A current review

“…Damage-associated molecular patterns (DAMPs) seem to play an important role in the communication of this stress system-wide and at different organism levels from plants to humans. 26,27 The spectrum of non-targeted effects still continues to broaden; currently it includes many types of exogenous and endogenous stressors that induce a systemic genotoxic response with the oxidative mechanisms holding a pivotal role.…”

“…The inflammasome is the molecular complex responsible for the processing of IL-1β before its secretion, as revealed by the proteolytic activation of caspase 1 in irradiated mice. 108 The activation of one of the most well-known inflammasomes, NLRP3, has been associated with various danger signals (PAMPs, DAMPs), 26 linked to innate and adaptive immune responses against dying tumor cells 109 and acceleration of radiation-induced lung inflammation and fibrosis in mice. 110 To this direction, it has been shown that low doses of X-rays (0.5 or 0.7 Gy) induce an antiinflammatory phenotype of activated macrophages by lowering the amount of secreted IL-1beta in a NF-kappaB dependent manner.…”