{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:49:55Z","timestamp":1788904195498,"version":"build-2803163510"},"reference-count":354,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T00:00:00Z","timestamp":1708300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The coronavirus disease 2019 (COVID-19) pandemic triggered an unprecedented concentration of economic and research efforts to generate knowledge at unequalled speed on deregulated interferon type I signalling and nuclear factor kappa light chain enhancer in B-cells (NF-\u03baB)-driven interleukin (IL)-1\u03b2, IL-6, IL-18 secretion causing cytokine storms. The translation of the knowledge on how the resulting systemic inflammation can lead to life-threatening complications into novel treatments and vaccine technologies is underway. Nevertheless, previously existing knowledge on the role of cytoplasmatic or circulating self-DNA as a pro-inflammatory damage-associated molecular pattern (DAMP) was largely ignored. Pathologies reported \u2018<jats:italic>de novo<\/jats:italic>\u2019 for patients infected with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 to be outcomes of self-DNA-driven inflammation in fact had been linked earlier to self-DNA in different contexts, e.g., the infection with Human Immunodeficiency Virus (HIV)-1, sterile inflammation, and autoimmune diseases. I highlight particularly how synergies with other DAMPs can render immunogenic properties to normally non-immunogenic extracellular self-DNA, and I discuss the shared features of the gp41 unit of the HIV-1 envelope protein and the SARS-CoV 2 Spike protein that enable HIV-1 and SARS-CoV-2 to interact with cell or nuclear membranes, trigger syncytia formation, inflict damage to their host\u2019s DNA, and trigger inflammation \u2013 likely for their own benefit. These similarities motivate speculations that similar mechanisms to those driven by gp41 can explain how inflammatory self-DNA contributes to some of most frequent adverse events after vaccination with the BNT162b2 mRNA (Pfizer\/BioNTech) or the mRNA-1273 (Moderna) vaccine, i.e., myocarditis, herpes zoster, rheumatoid arthritis, autoimmune nephritis or hepatitis, new-onset systemic lupus erythematosus, and flare-ups of psoriasis or lupus. The hope is to motivate a wider application of the lessons learned from the experiences with COVID-19 and the new mRNA vaccines to combat future non-COVID-19 diseases.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1259879","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T10:52:20Z","timestamp":1708339940000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Self-DNA driven inflammation in COVID-19 and after mRNA-based vaccination: lessons for non-COVID-19 pathologies"],"prefix":"10.3389","volume":"14","author":[{"given":"Martin","family":"Heil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.09.001","article-title":"Common senses","volume":"38","author":"Deguine","year":"2017","journal-title":"Trends 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