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Contemporary zoonotic infections with <jats:italic>Y. pestis<\/jats:italic> still occur in sub-Saharan Africa, including Tanzania and Madagascar, but receive relatively little attention. Thus, the role of wildlife reservoirs in maintaining sylvatic plague and spillover risks to humans is largely unknown. The multimammate rodent <jats:italic>Mastomys natalensis<\/jats:italic> is the most abundant and widespread rodent in peri-domestic areas in Tanzania, where it plays a major role as a <jats:italic>Y. pestis<\/jats:italic> reservoir in endemic foci. Yet, how <jats:italic>M. natalensis<\/jats:italic>\u2019 immunogenetics contributes to the maintenance of plague has not been investigated to date. Here, we surveyed wild <jats:italic>M. natalensis<\/jats:italic> for <jats:italic>Y. pestis<\/jats:italic> vectors, i.e., fleas, and tested for the presence of antibodies against <jats:italic>Y. pestis<\/jats:italic> using enzyme-linked immunosorbent assays (ELISA) in areas known to be endemic or without previous records of <jats:italic>Y. pestis<\/jats:italic> in Tanzania. We characterized the allelic and functional (i.e., supertype) diversity of the major histocompatibility complex (MHC class II) of <jats:italic>M. natalensis<\/jats:italic> and investigated links to <jats:italic>Y. pestis<\/jats:italic> vectors and infections. We detected antibodies against <jats:italic>Y. pestis<\/jats:italic> in rodents inhabiting both endemic areas and areas considered non-endemic. Of the 111 nucleotide MHC alleles, only <jats:italic>DRB*016<\/jats:italic> was associated with an increased infestation with the flea <jats:italic>Xenopsylla<\/jats:italic>. Surprisingly, we found no link between MHC alleles or supertypes and antibodies of <jats:italic>Y. pestis<\/jats:italic>. Our findings hint, however, at local adaptations towards <jats:italic>Y. pestis<\/jats:italic> vectors, an observation that more exhaustive sampling could unwind in the future.<\/jats:p>","DOI":"10.1007\/s00251-023-01323-7","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T03:27:52Z","timestamp":1697686072000},"page":"517-530","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immunogenetics, sylvatic plague and its vectors: insights from the pathogen reservoir Mastomys natalensis in Tanzania"],"prefix":"10.1007","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7296-1738","authenticated-orcid":false,"given":"Lavinia","family":"Haikukutu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Japhet R.","family":"Lyaku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles M.","family":"Lyimo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seth J.","family":"Eiseb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhodes H.","family":"Makundi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayodeji","family":"Olayemi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Wilhelm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"M\u00fcller-Klein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik W.","family":"Schmid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramona","family":"Fleischer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Sommer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,10,19]]},"reference":[{"key":"1323_CR1","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1186\/s13104-018-3984-3","volume":"11","author":"V Andrianaivoarimanana","year":"2018","unstructured":"Andrianaivoarimanana V, Rajerison M, Jambou R (2018) Exposure to Yersinia pestis increases resistance to plague in black rats and modulates transmission in Madagascar. 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