Dataset Information

Identification of lipophilic ligands of Siglec5 and -14 that modulate innate immune responses.

ABSTRACT: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of cell-surface immune receptors that bind to sialic acid at terminal glycan residues. Siglecs also recognize nonsialic acid ligands, many of which remain to be characterized. Here, we found that Siglec5 and Siglec14 recognize lipid compounds produced by Trichophyton, a fungal genus containing several pathogenic species. Biochemical approaches revealed that the Siglec ligands are fungal alkanes and triacylglycerols, an unexpected finding that prompted us to search for endogenous lipid ligands of Siglecs. Siglec5 weakly recognized several endogenous lipids, but the mitochondrial lipid cardiolipin and the anti-inflammatory lipid 5-palmitic acid-hydroxystearic acid exhibited potent ligand activity on Siglec5. Further, the hydrophobic stretch in the Siglec5 N terminus region was found to be required for efficient recognition of these lipids. Notably, this hydrophobic stretch was dispensable for recognition of sialic acid. Siglec5 inhibited cell activation upon ligand binding, and accordingly, the lipophilic ligands suppressed interleukin-8 (IL-8) production in Siglec5-expressing human monocytic cells. Siglec14 and Siglec5 have high sequence identity in the extracellular region, and Siglec14 also recognized the endogenous lipids. However, unlike Siglec5, Siglec14 transduces activating signals upon ligand recognition. Indeed, the endogenous lipids induced IL-8 production in Siglec14-expressing human monocytic cells. These results indicated that Siglec5 and Siglec14 can recognize lipophilic ligands that thereby modulate innate immune responses. To our knowledge, this is the first study reporting the binding of Siglecs to lipid ligands, expanding our understanding of the biological function and importance of Siglecs in the innate immunity.

SUBMITTER: Suematsu R

PROVIDER: S-EPMC6851322 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of lipophilic ligands of Siglec5 and -14 that modulate innate immune responses.

Suematsu Rie R Miyamoto Tomofumi T Saijo Shinobu S Yamasaki Sho S Tada Yoshifumi Y Yoshida Hiroki H Miyake Yasunobu Y

The Journal of biological chemistry 20190924 45

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of cell-surface immune receptors that bind to sialic acid at terminal glycan residues. Siglecs also recognize nonsialic acid ligands, many of which remain to be characterized. Here, we found that Siglec5 and Siglec14 recognize lipid compounds produced by <i>Trichophyton</i>, a fungal genus containing several pathogenic species. Biochemical approaches revealed that the Siglec ligands are fungal alkanes and triacylglycerols, an ...[more]

PMID: 31551352

Similar Datasets

Project description:Prevalence of the members of herpesvirus family in oral inflammatory diseases is increasingly acknowledged suggesting their likely role as an etiological factor. However, the underlying mechanisms remain obscure. In our recent miRNA profiling of healthy and diseased human tooth pulps, elevated expression of human herpesvirus encoded viral microRNAs (v-miRs) were identified. Based on the fold induction and significance values, we selected three v-miRs namely miR-K12-3-3p [Kaposi sarcoma-associated virus (KSHV)], miR-H1 [herpes simplex virus 1 (HSV1)], and miR-UL-70-3p [human cytomegalovirus (HCMV)] to further examine their impact on host cellular functions. We examined their impact on cellular miRNA profiles of primary human oral keratinocytes (HOK). Our results show differential expression of several host miRNAs in v-miR-transfected HOK. High levels of v-miRs were detected in exosomes derived from v-miR transfected HOK as well as the KSHV-infected cell lines. We show that HOK-derived exosomes release their contents into macrophages (Mφ) and alter expression of endogenous miRNAs. Concurrent expression analysis of precursor (pre)-miRNA and mature miRNA suggest transcriptional or posttranscriptional impact of v-miRs on the cellular miRNAs. Employing bioinformatics, we predicted several pathways targeted by deregulated cellular miRNAs that include cytoskeletal organization, endocytosis, and cellular signaling. We validated three novel targets of miR-K12-3-3p and miR-H1 that are involved in endocytic and intracellular trafficking pathways. To evaluate the functional consequence of this regulation, we performed phagocytic uptake of labeled bacteria and noticed significant attenuation in miR-H1 and miR-K12-3-3p but not miR-UL70-3p transfected primary human Mφ. Multiple cytokine analysis of E. coli challenged Mφ revealed marked reduction of secreted cytokine levels with important roles in innate and adaptive immune responses suggesting a role of v-miRs in immune subversion. Our findings reveal that oral disease associated v-miRs can dysregulate functions of key host cells that shape oral mucosal immunity thus exacerbating disease severity and progression.

Dataset Information

Identification of lipophilic ligands of Siglec5 and -14 that modulate innate immune responses.

Publications

Identification of lipophilic ligands of Siglec5 and -14 that modulate innate immune responses.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets