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In this study, we show that natural IgM antibodies targeting these fungal cell wall carbohydrates are conserved across many species, including fish and mammals. Natural antibodies bind fungal organisms and enhance host defense against Pneumocystis in early stages of infection. IgM antibodies influence recognition of fungal antigen by dendritic cells, increasing their migration to draining pulmonary lymph nodes. IgM antibodies are required for adaptive T helper type 2 (Th2) and Th17 cell differentiation and guide B cell isotype class-switch recombination during host defense against Pneumocystis. These experiments suggest a novel role for the IgM isotype in shaping the earliest steps in recognition and clearance of this fungus. We outline a mechanism whereby serum IgM, containing ancient specificities against conserved fungal antigens, bridges innate and adaptive immunity against fungal organisms.<\/jats:p>","DOI":"10.1084\/jem.20100034","type":"journal-article","created":{"date-parts":[[2010,12,13]],"date-time":"2010-12-13T23:41:20Z","timestamp":1292283680000},"page":"2907-2919","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":119,"title":["Conserved natural IgM antibodies mediate innate and adaptive immunity against the opportunistic fungus\n                    <i>Pneumocystis murina<\/i>"],"prefix":"10.1084","volume":"207","author":[{"given":"Rekha R.","family":"Rapaka","sequence":"first","affiliation":[{"name":"Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Ricks","sequence":"additional","affiliation":[{"name":"Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Alcorn","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabaana A.","family":"Khader","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingquan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Plevy","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Bengt\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Mississippi Medical Center, Jackson, MS 39216 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay K.","family":"Kolls","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224 1"},{"name":"Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2010,12,13]]},"reference":[{"key":"2023072617120841600_bib1","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/nm1710","article-title":"IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia","volume":"14","author":"Aujla","year":"2008","journal-title":"Nat. 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