{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:45:54Z","timestamp":1788410754386,"version":"build-2803163510"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"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>Outbreaks of infectious diseases repeatedly affected medieval Europe, leaving behind a large number of dead often inhumed in mass graves. Human remains interred in two burial pits from 14<jats:sup>th<\/jats:sup> century CE Germany exhibited molecular evidence of <jats:italic>Salmonella enterica<\/jats:italic> Paratyphi C (<jats:italic>S.<\/jats:italic> Paratyphi C) infection. The pathogen is responsible for paratyphoid fever, which was likely the cause of death for the buried individuals. This finding presented the unique opportunity to conduct a paratyphoid fever association study in a European population. We focused on HLA-DRB1*03:01 that is a known risk allele for enteric fever in present-day South Asians. We generated HLA profiles for 29 medieval <jats:italic>S.<\/jats:italic> Paratyphi C cases and 24 contemporaneous controls and compared these to a modern German population. The frequency of the risk allele was higher in the medieval cases (29.6%) compared to the contemporaneous controls (13%; <jats:italic>p = 0.189<\/jats:italic>), albeit not significantly so, possibly because of small sample sizes. Indeed, in comparison with the modern controls (<jats:italic>n = 39,689<\/jats:italic>; 10.2%; <jats:italic>p = 0.005<\/jats:italic>) the frequency difference became statistically significant. This comparison also suggested a slight decrease in the allele\u2019s prevalence between the medieval and modern controls. Up to now, this is the first study on the genetic predisposition to <jats:italic>Salmonella<\/jats:italic> infection in Europeans and the only association analysis on paratyphoid fever C. Functional investigation using computational binding prediction between HLA variants and <jats:italic>S.<\/jats:italic> Paratyphi and <jats:italic>S.<\/jats:italic> Typhi peptides supported a reduced recognition capacity of bacterial proteins by DRB1*03:01 relative to other common DRB1 variants. This pattern could potentially explain the disease association. Our results suggest a slightly reduced predisposition to paratyphoid fever in modern Europeans. The causative allele, however, is still common today, which can be explained by a trade-off, as DRB1*03:01 is protective against infectious respiratory diseases such as severe respiratory syndrome (SARS). It is thus possible that the allele also provided resistance to corona-like viruses in the past.<\/jats:p>","DOI":"10.3389\/fimmu.2021.691475","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T17:43:59Z","timestamp":1626371039000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Ancient DNA Study in Medieval Europeans Shows an Association Between HLA-DRB1*03 and Paratyphoid Fever"],"prefix":"10.3389","volume":"12","author":[{"given":"Magdalena","family":"Haller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna H.","family":"Bonczarowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Rieger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias L.","family":"Lenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almut","family":"Nebel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Krause-Kyora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/ajpa.20085","article-title":"Leprosy and Mortality in the Medieval Danish Village of Tirup","volume":"126","author":"Boldsen","year":"2005","journal-title":"Am J Phys Anthropol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpp.2018.11.003","article-title":"Tuberculosis in Medieval and Early Modern Denmark: A Paleoepidemiological Perspective","volume":"27","author":"Dangvard Pedersen","year":"2019","journal-title":"Int J Paleopathol"},{"key":"B3","doi-asserted-by":"crossref","first-page":"415 p","DOI":"10.7208\/chicago\/9780226189529.001.0001","volume-title":"Greatest Killer: Smallpox in History","author":"Hopkins","year":"2002"},{"key":"B4","doi-asserted-by":"publisher","first-page":"eaaw8977","DOI":"10.1126\/science.aaw8977","article-title":"Diverse Variola Virus (Smallpox) Strains Were Widespread in Northern Europe in the Viking Age","volume":"369","author":"M\u00fchlemann","year":"2020","journal-title":"Science"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e1006997","DOI":"10.1371\/journal.ppat.1006997","article-title":"Ancient Genomes Reveal a High Diversity of Mycobacterium Leprae in Medieval Europe","volume":"14","author":"Schuenemann","year":"2018","journal-title":"PloS Pathog"},{"key":"B6","doi-asserted-by":"publisher","first-page":"4470","DOI":"10.1038\/s41467-019-12154-0","article-title":"Phylogeography of the Second Plague Pandemic Revealed Through Analysis of Historical Yersinia Pestis Genomes","volume":"10","author":"Spyrou","year":"2019","journal-title":"Nat Commun"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.15184\/aqy.2019.213","article-title":"A Black Death Mass Grave at Thornton Abbey: The Discovery and Examination of a Fourteenth-Century Rural Catastrophe","volume":"94","author":"Willmott","year":"2020","journal-title":"Antiquity"},{"key":"B8","first-page":"139","article-title":"Arch\u00e4ologische Untersuchungen der Massenbestattungen am Heiligen-Geist-Hospital zu L\u00fcbeck: Auswertung der Befunde und Funde","volume-title":"L\u00fcbecker Schriften zu Arch\u00e4ologie und Kulturgeschichte 26","author":"L\u00fctgert","year":"2002"},{"key":"B9","article-title":"Anthropologische Untersuchungen der Skelettreste aus einem Pestmassengrab am Heiligen-Geist-Hospital zu L\u00fcbeck","volume-title":"L\u00fcbecker Schriften zu Arch\u00e4ologie und Kulturgeschichte 24","author":"Prechel","year":"1996"},{"key":"B10","article-title":"Eine L\u00fcbecker Population von 1350. 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