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Binding assays implementing soluble Mincle carbohydrate recognition domain fusion proteins demonstrated binding to intact Pneumocystis carinii as well as to organism homogenates, and they purified major surface glycoprotein\/glycoprotein A derived from the organism. Additional experiments showed that rats with PCP expressed increased Mincle mRNA levels. Mouse macrophages overexpressing Mincle displayed increased binding to P. carinii life forms and enhanced protein tyrosine phosphorylation. The binding of P. carinii to Mincle resulted in activation of FcR\u03b3-mediated cell signaling. RNA silencing of Mincle in mouse macrophages resulted in decreased activation of Syk kinase after P. carinii challenge, critical in downstream inflammatory signaling. Mincle-deficient CD4-depleted (Mincle\u2212\/\u2212) mice showed a significant defect in organism clearance from the lungs with higher organism burdens and altered lung cytokine responses during Pneumocystis murina pneumonia. Interestingly, Mincle\u2212\/\u2212 mice did not demonstrate worsened survival during PCP compared with wild-type mice, despite the markedly increased organism burdens. This may be related to increased expression of anti-inflammatory factors such as IL-1Ra during infection in the Mincle\u2212\/\u2212 mice. Of note, the P. murina\u2013infected Mincle\u2212\/\u2212 mice demonstrated increased expression of known C-type lectin receptors Dectin-1, Dectin-2, and MCL compared with infected wild-type mice. Taken together, these data support a significant role for Mincle in Pneumocystis modulating host defense during infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1600744","type":"journal-article","created":{"date-parts":[[2017,3,16]],"date-time":"2017-03-16T00:50:20Z","timestamp":1489625420000},"page":"3515-3525","source":"Crossref","is-referenced-by-count":51,"title":["The Interaction of <i>Pneumocystis<\/i> with the C-Type Lectin Receptor Mincle Exerts a Significant Role in Host Defense against Infection"],"prefix":"10.1093","volume":"198","author":[{"given":"Theodore J","family":"Kottom","sequence":"first","affiliation":[{"name":"Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic College of Medicine , Rochester, MN 55905"},{"name":"Department of Biochemistry, Mayo Clinic College of Medicine , Rochester, MN 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanne M","family":"Hebrink","sequence":"additional","affiliation":[{"name":"Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic College of Medicine , Rochester, MN 55905"},{"name":"Department of Biochemistry, Mayo Clinic College of Medicine , Rochester, MN 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige E","family":"Jenson","sequence":"additional","affiliation":[{"name":"Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic College of Medicine , Rochester, MN 55905"},{"name":"Department of Biochemistry, Mayo Clinic College of Medicine , Rochester, MN 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijayalakshmi","family":"Nandakumar","sequence":"additional","affiliation":[{"name":"Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic College of Medicine , Rochester, MN 55905"},{"name":"Department of Biochemistry, Mayo Clinic College of Medicine , Rochester, MN 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"W\u00fcthrich","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2002-4125","authenticated-orcid":false,"given":"Huafeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"},{"name":"Department of Internal Medicine, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"},{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University , Fukuoka 812-8582,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Lepenies","sequence":"additional","affiliation":[{"name":"University of Veterinary Medicine Hannover , Foundation, Hannover 30559,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H","family":"Limper","sequence":"additional","affiliation":[{"name":"Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic College of Medicine , Rochester, MN 55905"},{"name":"Department of Biochemistry, Mayo Clinic College of Medicine , Rochester, MN 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,5,1]]},"reference":[{"key":"2025030615120209000_r1","doi-asserted-by":"crossref","first-page":"fov046","DOI":"10.1093\/femsyr\/fov046","article-title":"Pathobiology of Pneumocystis pneumonia: life cycle, cell wall and cell signal transduction","volume":"15","author":"Skalski","year":"2015","journal-title":"FEMS Yeast Res."},{"key":"2025030615120209000_r2","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1056\/NEJMra032588","article-title":"Pneumocystis pneumonia","volume":"350","author":"Thomas","year":"2004","journal-title":"N. 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