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Host sensing of corynebacteria is largely uncharacterized, albeit the recognition of lipoglycans by Toll-like receptor 2 (TLR2) appears to be important for macrophage activation by corynebacteria. The members of the order<jats:named-content content-type=\"genus-species\">Corynebacterineae<\/jats:named-content>(e.g., mycobacteria, nocardia, and rhodococci) share a glycolipid-rich cell wall dominated by mycolic acids (termed corynomycolic acids in corynebacteria). The mycolic acid-containing cord factor of mycobacteria, trehalose dimycolate, activates the C-type lectin receptor (CLR) Mincle. Here, we show that glycolipid extracts from the cell walls of several pathogenic and nonpathogenic<jats:named-content content-type=\"genus-species\">Corynebacterium<\/jats:named-content>strains directly bound to recombinant Mincle<jats:italic>in vitro<\/jats:italic>. Macrophages deficient in Mincle or its adapter protein Fc receptor gamma chain (FcR\u03b3) produced severely reduced amounts of granulocyte colony-stimulating factor (G-CSF) and of nitric oxide (NO) upon challenge with corynebacterial glycolipids. Consistently, cell wall extracts of a particular<jats:named-content content-type=\"genus-species\">C. diphtheriae<\/jats:named-content>strain (DSM43989) lacking mycolic acid esters neither bound Mincle nor activated macrophages. Furthermore, TLR2 but not TLR4 was critical for sensing of cell wall extracts and whole corynebacteria. The upregulation of Mincle expression upon encountering corynebacteria required TLR2. Thus, macrophage activation by the corynebacterial cell wall relies on TLR2-driven robust Mincle expression and the cooperative action of both receptors.<\/jats:p>","DOI":"10.1128\/iai.00075-17","type":"journal-article","created":{"date-parts":[[2017,5,9]],"date-time":"2017-05-09T00:40:25Z","timestamp":1494290425000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["Toll-Like Receptor 2 and Mincle Cooperatively Sense Corynebacterial Cell Wall Glycolipids"],"prefix":"10.1128","volume":"85","author":[{"given":"Judith","family":"Schick","sequence":"first","affiliation":[{"name":"Institute of Clinical Microbiology, Immunology and Hygiene, Universit\u00e4tsklinikum Erlangen, Friedrich Alexander Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Etschel","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology, Immunology and Hygiene, Universit\u00e4tsklinikum Erlangen, Friedrich Alexander Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca","family":"Bailo","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Ott","sequence":"additional","affiliation":[{"name":"Microbiology Division, Department Biologie, Friedrich Alexander Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apoorva","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Lepenies","sequence":"additional","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses, Tier\u00e4rztliche Hochschule Hannover, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Kirschning","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1896-4521","authenticated-orcid":false,"given":"Andreas","family":"Burkovski","sequence":"additional","affiliation":[{"name":"Microbiology Division, Department Biologie, Friedrich Alexander Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0502-3677","authenticated-orcid":false,"given":"Roland","family":"Lang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology, Immunology and Hygiene, Universit\u00e4tsklinikum Erlangen, Friedrich Alexander Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.43.3.1114-1116.1984"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1051\/vetres:2005056"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2016-0085"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES2014.19.22.20819"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1911.130297"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsle\/fnv185"},{"key":"e_1_3_3_8_2","first-page":"525","article-title":"Percutaneous nephrostomy tube-associated bacteremia caused by Corynebacterium urealyticum","volume":"41","author":"Chung CS","year":"2008","unstructured":"Chung CS Liao CH Cheng SL Lin TH Hsueh PR . 2008. 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