Role of Damage-Associated Molecular Patterns in Light of Modern Environmental Research: A Tautological Approach

Abstract

Two prominent models emerged as a result of intense interdisciplinary discussions on the environmental health paradigm, called the "exposome" concept and the "adverse outcome pathway" (AOP) concept that links a molecular initiating event to the adverse outcome via key events. Here, evidence is discussed, suggesting that environmental stress/injury-induced damageassociated molecular patterns (DAMPs) may operate as an essential integrating element of both environmental health research paradigms. DAMP-promoted controlled/uncontrolled innate/adaptive immune responses reflect the key events of the AOP concept. The whole process starting from exposure to a distinct environmental stress/injury-associated with the presence/ emission of DAMPs-up to the manifestation of a disease may be regarded as an exposome. Clinical examples of such a scenario are briefly sketched, in particular, a model in relation to the emerging COVID-19 pandemic, where the interaction of noninfectious environmental factors (e.g., particulate matter) and infectious factors (SARS CoV-2) may promote SARS case fatality via superimposition of both exogenous and endogenous DAMPs. Article Highlights • This review is devoted to the first scientific attempt to integrate DAMP-controlled innate immune inflammatory and adaptive immune defense responses as well as DAMP-uncontrolled dysregulated pathological responses (acute and chronic human diseases) in the environmental health paradigm, called the "exposome" concept and the "adverse outcome pathway" (AOP) concept. • Evidence is discussed that DAMP-promoted controlled/uncontrolled innate immune/adaptive immune responses reflect the key events of the AOP concept. • The whole process starting from exposure to a distinct environmental stress/injury-associated with the presence/ emission of DAMPs-up to the manifestation of a disease may be regarded as an exposome. • Some exemplifying models of such a scenario are briefly sketched, including respiratory infections, autoimmune/ allergic diseases, organ fibrosis, and cancer. • In particular, a model in relation to the emerging COVID-19 pandemic is presented, where the interaction of noninfectious environmental factors (e.g., particulate matter) and infectious factors (SARS CoV-2) may promote SARS case fatality via superimposition of both exogenous and endogenous DAMPs.

Why Is COVID-19 More Severe in Patients With Diabetes? The Role of Angiotensin-Converting Enzyme 2, Endothelial Dysfunction and the Immunoinflammatory System

“…Older patients with COVID-19 can reduce their viral titres, only to rapidly descend into a state of shock due to hyperactivation of the immune system, known as a cytokine storm. One mechanism by which this might occur is via virus-injured cells releasing the DAMPs that can promote hyperinflammation ( 222 , 223 ).…”

Trends and challenges in phytotherapy and phytocosmetics for skin aging

“…Sterile inflammation otherwise known as chronic low level or pathogen-free inflammation can also be induced by some sterile stimuli such as certain environmental cues, ischemia, mechanical trauma, and stress. These stimuli lead to the secretion of damage-associated molecular patterns (DAMPs) which are responsible for the activation of some innate immune effectors such as families of NOD-like and toll-like receptors ( Feldman et al, 2015 , Land, 2020 , Relja and Land, 2020 ). The prolonged inflammation is also linked to the overproduction of mediators such as inducible type cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukins (IL 1β, IL-6, IL-8), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor (TNF-α), nuclear factor-κB (NF-κB), prostaglandin E2 (PGE2), and 5-lipoxygenase (5-LOX) by the pro-inflammatory and immune cells such as macrophages and monocytes ( Fig.…”

Exposome-based public health interventions for infectious diseases in urban settings

“…Notwithstanding, there were two studies that included measurements of pathogens as exposures in personal exposure monitoring schemes ( Cissé et al, 2020 , Jiang et al, 2018 ). Moreover, infectious diseases have been described as components of the mixture of exposures in association with physiological aspects of infection to SARS-CoV-2 in a commentary and a review article ( Land, 2020 , Naughton et al, 2020 ). So far, the exposome concept has predominantly found use in exposure science and environmental health.…”