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The reasons for the high susceptibility of AD patients to microbial infections are still unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The influence of self\u2010DNA on the antimicrobial activity of RNase 7, LL\u201037, and hBD2\u00a0has been investigated using antibacterial and antiviral assays. The amount of self\u2010DNA on skin has been analyzed by skin rinsings and subsequent quantification using dsDNA assays. DNA source was identified by qPCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Complex formation of the AMPs with self\u2010DNA significantly impaired their antibacterial activity against<jats:italic>Staphylococcus aureus<\/jats:italic>and their antiviral activity against<jats:italic>HSV<\/jats:italic>\u2010<jats:italic>1<\/jats:italic>. The inhibition of the antibacterial activity was dependent on the DNA concentration but not on the length of the DNA molecules. Of note, we detected significant higher amounts of cell\u2010free self\u2010DNA in skin rinses taken from lesional AD skin compared to skin rinses from non\u2010lesional skin and from normal skin of healthy donors. Consequently, rinse solution from AD lesional skin prevented antibacterial activity of LL\u201037.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study indicates that extracellular self\u2010DNA is released in considerable amounts in AD skin lesions and AMP\u2010self\u2010DNA\u2010complex formation leads to a significant loss of antibacterial and antiviral activity in atopic dermatitis. Studies on strategies to reduce the amount of extracellular DNA in AD are needed to identify possible methods relevant in clinical settings.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.14992","type":"journal-article","created":{"date-parts":[[2021,6,27]],"date-time":"2021-06-27T18:49:05Z","timestamp":1624819745000},"page":"3145-3154","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Free human DNA attenuates the activity of antimicrobial peptides in atopic dermatitis"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2060-5643","authenticated-orcid":false,"given":"Verena","family":"Kopfnagel","sequence":"first","affiliation":[{"name":"Division of Immunodermatology and Allergy Research Department of Dermatology and Allergy Hannover Medical School Hannover Germany"},{"name":"Cluster of Excellence RESIST (EXC 2155) Hannover Medical School Hannover 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