{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:07:03Z","timestamp":1790514423044,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2010,12,1]],"date-time":"2010-12-01T00:00:00Z","timestamp":1291161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Although transmembrane C-type lectins (CLs) are known to initiate immune signaling, the participation and mechanism of action of soluble CLs have remained enigmatic. In this study, we found that M-ficolin, a conserved soluble CL of monocyte origin, overcomes its lack of membrane-anchor domain by docking constitutively onto a monocyte transmembrane receptor, G protein-coupled receptor 43 (GPCR43), to form a pathogen sensor-cum-signal transducer. On encountering microbial invaders, the M-ficolin\u2013GPCR43 complex activates the NF-\u03baB cascade to upregulate IL-8 production. We showed that mild acidosis at the local site of infection induces conformational changes in the M-ficolin molecule, which provokes a strong interaction between the C-reactive protein (CRP) and the M-ficolin\u2013GPCR43 complex. The collaboration among CRP\u2013M-ficolin\u2013GPCR43 under acidosis curtails IL-8 production thus preventing immune overactivation. Therefore, we propose that a soluble CL may become membrane-associated through interaction with a transmembrane protein, whereupon infection collaborates with other plasma protein to transduce the infection signal and regulate host defense. Our finding implies a possible mechanism whereby the host might expand its repertoire of immune recognition-cum-regulation tactics by promiscuous protein networking. Furthermore, our identification of the pH-sensitive interfaces of M-ficolin\u2013CRP provides a powerful template for future design of potential immunomodulators.<\/jats:p>","DOI":"10.4049\/jimmunol.1001225","type":"journal-article","created":{"date-parts":[[2010,10,30]],"date-time":"2010-10-30T03:06:24Z","timestamp":1288407984000},"page":"6899-6910","source":"Crossref","is-referenced-by-count":63,"title":["Secreted M-Ficolin Anchors onto Monocyte Transmembrane G Protein-Coupled Receptor 43 and Cross Talks with Plasma C-Reactive Protein to Mediate Immune Signaling and Regulate Host Defense"],"prefix":"10.1093","volume":"185","author":[{"given":"Jing","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Graduate School for Integrative Science and Engineerin ,","place":["Singapore 117543"]},{"name":"Graduate School for Integrative Science and Engineering ,","place":["Singapore 117543"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Graduate School for Integrative Science and Engineerin ,","place":["Singapore 117543"]},{"name":"Singapore\u2013Massachusetts Institute of Technology Alliance ,","place":["Singapore 117543"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Ang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Graduate School for Integrative Science and Engineerin ,","place":["Singapore 117543"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sia Lee","family":"Yoong","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Graduate School for Integrative Science and Engineerin ,","place":["Singapore 117543"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Thu Thuy","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Graduate School for Integrative Science and Engineerin ,","place":["Singapore 117543"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh Srinivasan","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Graduate School for Integrative Science and Engineerin ,","place":["Singapore 117543"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguan Soon","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University ,","place":["Singapore 639798"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bow","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Microbiology, National University of Singapore ,","place":["Singapore 117543"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeak Ling","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Graduate School for Integrative Science and Engineerin ,","place":["Singapore 117543"]},{"name":"Singapore\u2013Massachusetts Institute of Technology Alliance ,","place":["Singapore 117543"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,12,1]]},"reference":[{"key":"2025032412121656600_r1","doi-asserted-by":"crossref","first-page":"4818","DOI":"10.1128\/IAI.68.8.4818-4821.2000","article-title":"Role of monocytes in experimental Staphylococcus aureus endocarditis","volume":"68","author":"Veltrop","year":"2000","journal-title":"Infect. 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