title: Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia.
abstract: The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. The T. forsythia S-layer has been implicated in the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis. The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. In this study, we aimed to determine if Mincle might be involved in the recognition of T. forsythia S-layer and modulation of cytokine response of macrophages against the bacterium. Binding studies using recombinant Mincle-Fc fusion protein indicated a specific Ca2+-dependent binding of Mincle to T. forsythia S-layer. Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages revealed a role for Mincle/S-layer interaction in the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia as well as its S-layer. Together, these studies revealed Mincle as an important macrophage receptor involved in the modulation of cytokine responses of macrophages against T. forsythia, and thus may play a critical role in orchestrating the host immune response against the bacterium.
authors.affiliation: Dept. of Oral Biology, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Sreedevi
authors.initials: S
authors.lastname: Chinthamani
authors.affiliation: Dept. of Oral Biology, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Rajendra P
authors.initials: RP
authors.lastname: Settem
authors.affiliation: Dept. of Oral Biology, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Kiyonobu
authors.initials: K
authors.lastname: Honma
authors.affiliation: Dept. of Oral Biology, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Kay
authors.affiliation: Dept. of Oral Biology, University at Buffalo, Buffalo, New York, United States of America.
authors.forename: Ashu
authors.identifier: http://orcid.org/0000-0001-9252-0668
authors.initials: A
authors.lastname: Sharma
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010518:Periodontitis / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D010587:Phagocytosis / Q000276:immunology; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D000070436:Tannerella forsythia / Q000276:immunology* / Q000378:metabolism* / Q000472:pathogenicity
chemical_list: D016207:Cytokines; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; C055764:S-layer proteins