{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T23:53:43Z","timestamp":1770681223996,"version":"3.49.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>TNF blockade constitutes an effective therapy for inflammatory bowel disease, yet increases the risk for infection, including active tuberculosis. The DECTIN2 family C-type lectin receptors MINCLE, MCL, and DECTIN2 sense mycobacterial ligands and activate myeloid cells. In mice, upregulation of DECTIN2 family C-type lectin receptor after stimulation with Mycobacterium bovis Bacille Calmette-Gu\u00e9rin requires TNF. Here, we investigated whether TNF controls inducible C-type lectin receptor expression in human myeloid cells. Monocyte-derived macrophages were stimulated with Bacille Calmette-Gu\u00e9rin and the TLR4 ligand lipopolysaccharide, and expression of C-type lectin receptor was analyzed. Bacille Calmette-Gu\u00e9rin and lipopolysaccharide strongly upregulated messenger RNA expression of DECTIN2 family C-type lectin receptor but not of DECTIN1. Bacille Calmette-Gu\u00e9rin and lipopolysaccharide also induced robust production of TNF. Recombinant TNF was sufficient to upregulate expression of DECTIN2 family C-type lectin receptor. Blocking TNF with the TNFR2-Fc fusion protein etanercept abrogated, as expected, the effect of recombinant TNF and impaired induction of DECTIN2 family C-type lectin receptor by Bacille Calmette-Gu\u00e9rin and lipopolysaccharide. Flow cytometry confirmed upregulation of MCL at the protein level by recombinant TNF and showed inhibition of Bacille Calmette-Gu\u00e9rin\u2013induced MCL by etanercept. To investigate the impact of TNF on C-type lectin receptor expression in vivo, we analyzed peripheral blood mononuclear cells of patients with inflammatory bowel disease and observed downregulation of MINCLE and MCL expression after therapeutic TNF blockade. Together, TNF is sufficient to upregulate DECTIN2 family C-type lectin receptor in human myeloid cells and contributes to this process after encounter with Bacille Calmette-Gu\u00e9rin or lipopolysaccharide. Impaired C-type lectin receptor expression in patients receiving TNF blockade may dampen the sensing of microbes and defense against infection.<\/jats:p>","DOI":"10.1093\/jleuko\/qiad029","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T13:58:42Z","timestamp":1678802322000},"page":"615-625","source":"Crossref","is-referenced-by-count":10,"title":["TNF promotes DECTIN2 family C-type lectin receptor expression in human macrophages"],"prefix":"10.1093","volume":"113","author":[{"given":"Carl","family":"Haberkamp","sequence":"first","affiliation":[{"name":"Institute of Clinical Microbiology, Immunology and Hygiene, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, Wasserturmstr. 3-5, 91054 Erlangen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ida","family":"Allabauer","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Endoscopy, Department of Pediatrics and Adolescent Medicine, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Loschgestr. 15, 91054 Erlangen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niklas","family":"Blaha","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology, Immunology and Hygiene, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, Wasserturmstr. 3-5, 91054 Erlangen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Bodendorfer","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology, Immunology and Hygiene, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, Wasserturmstr. 3-5, 91054 Erlangen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine and Hemostaseology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, Krankenhausstr. 12, 91054 Erlangen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre","family":"Hoerning","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Endoscopy, Department of Pediatrics and Adolescent Medicine, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Loschgestr. 15, 91054 Erlangen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Wasserturmstr. 3-5, 91054 Erlangen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,3,14]]},"reference":[{"issue":"6","key":"2023060100322580400_qiad029-B1","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/1074-7613(95)90001-2","article-title":"Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice","volume":"2","author":"Flynn","year":"1995","journal-title":"Immunity"},{"key":"2023060100322580400_qiad029-B2","doi-asserted-by":"crossref","first-page":"382","DOI":"10.3389\/fimmu.2019.00382","article-title":"Anti-TNF therapy in spondyloarthritis and related diseases, impact on the immune system and prediction of treatment responses","volume":"10","author":"Menegatti","year":"2019","journal-title":"Front Immunol"},{"issue":"9","key":"2023060100322580400_qiad029-B3","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/nri1184","article-title":"Signalling pathways of the TNF superfamily: a double-edged sword","volume":"3","author":"Aggarwal","year":"2003","journal-title":"Nat Rev Immunol"},{"issue":"8","key":"2023060100322580400_qiad029-B4","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/s41590-019-0415-0","article-title":"Targeting immune cell circuits and trafficking in inflammatory bowel disease","volume":"20","author":"Neurath","year":"2019","journal-title":"Nat Immunol"},{"issue":"7","key":"2023060100322580400_qiad029-B5","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1056\/NEJMra1909094","article-title":"Reframing immune-mediated inflammatory diseases through signature cytokine hubs","volume":"385","author":"Schett","year":"2021","journal-title":"N Engl J Med"},{"issue":"9","key":"2023060100322580400_qiad029-B6","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1136\/ard.62.9.829","article-title":"Systematic safety follow up in a cohort of 107 patients with spondyloarthropathy treated with infliximab: a new perspective on the role of host defence in the pathogenesis of the disease?","volume":"62","author":"Baeten","year":"2003","journal-title":"Ann Rheum Dis"},{"issue":"3","key":"2023060100322580400_qiad029-B7","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S1473-3099(03)00545-0","article-title":"Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management","volume":"3","author":"Gardam","year":"2003","journal-title":"Lancet Infect Dis"},{"issue":"Suppl 2","key":"2023060100322580400_qiad029-B8","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.cmi.2017.12.025","article-title":"ESCMID Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biological therapies: an infectious diseases perspective (soluble immune effector molecules [I]: anti-tumor necrosis factor-alpha agents)","volume":"24","author":"Baddley","year":"2018","journal-title":"Clin Microbiol Infect"},{"issue":"1","key":"2023060100322580400_qiad029-B9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/art.39480","article-title":"2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis","volume":"68","author":"Singh","year":"2016","journal-title":"Arthritis Rheumatol"},{"issue":"6","key":"2023060100322580400_qiad029-B10","doi-asserted-by":"crossref","first-page":"3504","DOI":"10.4049\/jimmunol.162.6.3504","article-title":"Structural deficiencies in granuloma formation in TNF gene-targeted mice underlie the heightened susceptibility to aerosol Mycobacterium tuberculosis infection, which is not compensated for by lymphotoxin","volume":"162","author":"Bean","year":"1999","journal-title":"J Immunol"},{"issue":"2","key":"2023060100322580400_qiad029-B11","doi-asserted-by":"crossref","first-page":"323","DOI":"10.4049\/jimmunol.2000420","article-title":"Cutting edge: TNF is essential for mycobacteria-induced MINCLE expression, macrophage activation, and Th17 adjuvanticity","volume":"205","author":"Schick","year":"2020","journal-title":"J Immunol"},{"issue":"4","key":"2023060100322580400_qiad029-B12","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.4049\/jimmunol.1601665","article-title":"Contact, collaboration, and conflict: signal integration of Syk-coupled C-type lectin receptors","volume":"198","author":"Ostrop","year":"2017","journal-title":"J Immunol"},{"issue":"4","key":"2023060100322580400_qiad029-B13","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.mib.2011.07.001","article-title":"The role of dectin-1 in the host defence against fungal infections","volume":"14","author":"Drummond","year":"2011","journal-title":"Curr Opin Microbiol"},{"issue":"6","key":"2023060100322580400_qiad029-B14","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.4049\/jimmunol.179.6.3463","article-title":"Dectin-1 interaction with Mycobacterium tuberculosis leads to enhanced IL-12p40 production by splenic dendritic cells","volume":"179","author":"Rothfuchs","year":"2007","journal-title":"J Immunol"},{"issue":"5","key":"2023060100322580400_qiad029-B15","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1093\/intimm\/dxt006","article-title":"The Dectin-2 family of C-type lectin-like receptors: an update","volume":"25","author":"Kerscher","year":"2013","journal-title":"Int Immunol"},{"issue":"13","key":"2023060100322580400_qiad029-B16","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1084\/jem.20091750","article-title":"Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle","volume":"206","author":"Ishikawa","year":"2009","journal-title":"J Exp Med"},{"issue":"5","key":"2023060100322580400_qiad029-B17","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.immuni.2013.03.010","article-title":"C-type lectin MCL is an FcR\u03b3-coupled receptor that mediates the adjuvanticity of mycobacterial cord factor","volume":"38","author":"Miyake","year":"2013","journal-title":"Immunity"},{"issue":"6","key":"2023060100322580400_qiad029-B18","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.4049\/jimmunol.0904013","article-title":"Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate","volume":"184","author":"Schoenen","year":"2010","journal-title":"J Immunol"},{"issue":"3","key":"2023060100322580400_qiad029-B19","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.immuni.2014.08.005","article-title":"Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria","volume":"41","author":"Yonekawa","year":"2014","journal-title":"Immunity"},{"issue":"1","key":"2023060100322580400_qiad029-B20","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.it.2016.10.009","article-title":"Recognition of mycobacterial lipids by immune receptors","volume":"38","author":"Ishikawa","year":"2017","journal-title":"Trends Immunol"},{"issue":"6","key":"2023060100322580400_qiad029-B21","doi-asserted-by":"crossref","first-page":"3121","DOI":"10.4049\/jimmunol.1201399","article-title":"Role of Mincle in alveolar macrophage-dependent innate immunity against mycobacterial infections in mice","volume":"189","author":"Behler","year":"2012","journal-title":"J Immunol"},{"issue":"4","key":"2023060100322580400_qiad029-B22","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.imbio.2012.06.005","article-title":"Mincle is not essential for controlling Mycobacterium tuberculosis infection","volume":"218","author":"Heitmann","year":"2013","journal-title":"Immunobiology"},{"issue":"2","key":"2023060100322580400_qiad029-B23","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.chom.2015.01.004","article-title":"The C-type lectin receptor CLECSF8\/CLEC4D is a key component of anti-mycobacterial immunity","volume":"17","author":"Wilson","year":"2015","journal-title":"Cell Host Microbe"},{"issue":"4","key":"2023060100322580400_qiad029-B24","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1084\/jem.20090067","article-title":"The adaptor molecule CARD9 is essential for tuberculosis control","volume":"207","author":"Dorhoi","year":"2010","journal-title":"J Exp Med"},{"issue":"5","key":"2023060100322580400_qiad029-B25","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.4049\/jimmunol.1500102","article-title":"Contribution of MINCLE-SYK signaling to activation of primary human APCs by mycobacterial cord factor and the novel adjuvant TDB","volume":"195","author":"Ostrop","year":"2015","journal-title":"J Immunol"},{"issue":"11","key":"2023060100322580400_qiad029-B26","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/j.imbio.2013.07.005","article-title":"Leukoreduction system chambers are an efficient, valid, and economic source of functional monocyte-derived dendritic cells and lymphocytes","volume":"218","author":"Pfeiffer","year":"2013","journal-title":"Immunobiology"},{"issue":"2","key":"2023060100322580400_qiad029-B27","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1189\/jlb.0105015","article-title":"Phenotypic and functional profiling of human proinflammatory type-1 and anti-inflammatory type-2 macrophages in response to microbial antigens and IFN-gamma- and CD40L-mediated costimulation","volume":"79","author":"Verreck","year":"2006","journal-title":"J Leukoc Biol"},{"issue":"7","key":"2023060100322580400_qiad029-B28","doi-asserted-by":"crossref","first-page":"3664","DOI":"10.4049\/jimmunol.1301593","article-title":"Differential control of Mincle-dependent cord factor recognition and macrophage responses by the transcription factors C\/EBP\u03b2 and HIF1\u03b1","volume":"193","author":"Schoenen","year":"2014","journal-title":"J Immunol"},{"issue":"9","key":"2023060100322580400_qiad029-B29","doi-asserted-by":"crossref","first-page":"5039","DOI":"10.4049\/jimmunol.163.9.5039","article-title":"A novel LPS-inducible C-type lectin is a transcriptional target of NF-IL6 in macrophages","volume":"163","author":"Matsumoto","year":"1999","journal-title":"J Immunol"},{"issue":"10","key":"2023060100322580400_qiad029-B30","doi-asserted-by":"crossref","first-page":"7681","DOI":"10.1167\/iovs.11-7999","article-title":"Effect of infliximab on gene expression profiling in Behcet's disease","volume":"52","author":"Keino","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"4","key":"2023060100322580400_qiad029-B31","doi-asserted-by":"crossref","first-page":"377","DOI":"10.5114\/ceji.2020.103411","article-title":"Expression and regulation of macrophage-inducible C-type lectin in human synovial macrophages","volume":"45","author":"Moriya","year":"2020","journal-title":"Cent Eur J Immunol"},{"issue":"8","key":"2023060100322580400_qiad029-B32","doi-asserted-by":"crossref","first-page":"e42656","DOI":"10.1371\/journal.pone.0042656","article-title":"In vitro generation of monocyte-derived macrophages under serum-free conditions improves their tumor promoting functions","volume":"7","author":"Rey-Giraud","year":"2012","journal-title":"PLoS One"},{"issue":"8","key":"2023060100322580400_qiad029-B33","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1073\/pnas.1222738110","article-title":"Conservation and divergence in the transcriptional programs of the human and mouse immune systems","volume":"110","author":"Shay","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023060100322580400_qiad029-B34","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.3389\/fimmu.2017.01864","article-title":"Review: impact of helminth infection on antimycobacterial immunity-A focus on the macrophage","volume":"8","author":"Lang","year":"2017","journal-title":"Front Immunol"},{"issue":"7","key":"2023060100322580400_qiad029-B35","doi-asserted-by":"crossref","first-page":"e20191692","DOI":"10.1084\/jem.20191692","article-title":"Efficient gene knockout in primary human and murine myeloid cells by non-viral delivery of CRISPR-Cas9","volume":"217","author":"Freund","year":"2020","journal-title":"J Exp Med"},{"key":"2023060100322580400_qiad029-B36","doi-asserted-by":"crossref","first-page":"656867","DOI":"10.3389\/fcell.2021.656867","article-title":"High-yield human induced pluripotent stem cell-derived monocytes and macrophages are functionally comparable with primary cells","volume":"9","author":"Cui","year":"2021","journal-title":"Front Cell Dev Biol"},{"issue":"1","key":"2023060100322580400_qiad029-B37","doi-asserted-by":"crossref","first-page":"22454","DOI":"10.1038\/srep22454","article-title":"Innate myeloid cell TNFR1 mediates first line defence against primary Mycobacterium tuberculosis infection","volume":"6","author":"Segueni","year":"2016","journal-title":"Sci Rep"},{"issue":"12","key":"2023060100322580400_qiad029-B38","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.4049\/jimmunol.2000509","article-title":"Overexpression of macrophage-inducible C-type lectin Mincle aggravates proinflammatory responses to Streptococcus pneumoniae with fatal outcome in mice","volume":"205","author":"Hollwedel","year":"2020","journal-title":"J Immunol"},{"issue":"12","key":"2023060100322580400_qiad029-B39","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1093\/ecco-jcc\/jjaa088","article-title":"Mincle\/Syk signalling promotes intestinal mucosal inflammation through induction of macrophage pyroptosis in Crohn's disease","volume":"14","author":"Gong","year":"2020","journal-title":"J Crohns Colitis"},{"issue":"2","key":"2023060100322580400_qiad029-B40","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.immuni.2018.12.020","article-title":"Microbiota sensing by Mincle-Syk axis in dendritic cells regulates interleukin-17 and \u221222 production and promotes intestinal barrier integrity","volume":"50","author":"Martinez-Lopez","year":"2019","journal-title":"Immunity"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jleukbio\/advance-article-pdf\/doi\/10.1093\/jleuko\/qiad029\/49654732\/qiad029.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/113\/6\/615\/50460562\/qiad029.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/113\/6\/615\/50460562\/qiad029.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:34:38Z","timestamp":1685579678000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/113\/6\/615\/7077207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,14]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3,14]]},"published-print":{"date-parts":[[2023,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jleuko\/qiad029","relation":{},"ISSN":["1938-3673"],"issn-type":[{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,6]]},"published":{"date-parts":[[2023,3,14]]}}}