Role of Damage-Associated Molecular Patterns in Light of Modern Environmental Research: A Tautological Approach
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REVIEW ARTICLE
Role of Damage‑Associated Molecular Patterns in Light of Modern Environmental Research: A Tautological Approach Walter Gottlieb Land1,2 Received: 13 May 2020 / Revised: 30 July 2020 / Accepted: 1 August 2020 © University of Tehran 2020
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
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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.
Keywords DAMPs · Innate immunity · Exposome · Adverse outcome pathway · COVID-19
* Walter Gottlieb Land [email protected] https://www.akademie-fuer-transplantationsmedizin.de/ 1
German Academy for Transplantation Medicine, Munich, Germany
Molecular ImmunoRheumatology, Laboratory of Excellence Transplantex, Faculty of Medicine, INSERM UMR_S1109, University of Strasbourg, Strasbourg, France
2
Introduction The most common diseas
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