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 damage-associated 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.