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Vsig4+ macrophages are key players preventing infiltration of bacteria and their products into host tissues. However, roles of islet Vsig4+ macrophages in the communication between microbiota and \u03b2 cells in pathogenesis of obesity-associated islet abnormalities are unknown. Here, we find that bacterial DNAs are enriched in \u03b2 cells of individuals with obesity. Intestinal microbial DNA-containing extracellular vesicles (mEVs) readily pass through obese gut barrier and deliver microbial DNAs into \u03b2 cells, resulting in elevated inflammation and impaired insulin secretion by triggering cGAS\/STING activation. Vsig4+ macrophages prevent mEV infiltration into \u03b2 cells through a C3-dependent opsonization, whereas loss of Vsig4 leads to microbial DNA enrichment in \u03b2 cells after mEV treatment. Removal of microbial DNAs blunts mEV effects. Loss of Vsig4+ macrophages leads to microbial DNA accumulation in \u03b2 cells and subsequently obesity-associated islet abnormalities.<\/jats:p>","DOI":"10.1038\/s41467-022-28239-2","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T11:03:34Z","timestamp":1643367814000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Accumulation of microbial DNAs promotes to islet inflammation and \u03b2 cell abnormalities in obesity in mice"],"prefix":"10.1038","volume":"13","author":[{"given":"Hong","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4323-2787","authenticated-orcid":false,"given":"Zhenlong","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1638-5497","authenticated-orcid":false,"given":"Yudong","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kechun","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongmou","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal","family":"Ly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9260-3540","authenticated-orcid":false,"given":"Dorothy D.","family":"Sears","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushil","family":"Mahata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4890-7256","authenticated-orcid":false,"given":"Wei","family":"Ying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"28239_CR1","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.cell.2017.12.025","volume":"172","author":"YS Lee","year":"2018","unstructured":"Lee, Y. 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