Toll-like receptors 2 and 4, and bacterial proteins in IgG4-related sialadenitis, other types of chronic sialadenitis and sialolithiasis

Background The association of chronic sclerosing sialadenitis and IgG4-related disease (IgG4-RD) has resulted in the more frequent identification of IgG4-positivity in submandibular gland inflammations, also uncovering IgG4 overexpression in nonspecific inflammations. These findings lead us to hypot...

Full description

Saved in:
Bibliographic Details
Main Authors: Elin Waltimo, Mine Eray, Antti Mäkitie, Caj Haglund, Timo Atula, Jaana Hagström
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Journal of Oral Microbiology
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/20002297.2024.2382633
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850269101051609088
author Elin Waltimo
Mine Eray
Antti Mäkitie
Caj Haglund
Timo Atula
Jaana Hagström
author_facet Elin Waltimo
Mine Eray
Antti Mäkitie
Caj Haglund
Timo Atula
Jaana Hagström
author_sort Elin Waltimo
collection DOAJ
description Background The association of chronic sclerosing sialadenitis and IgG4-related disease (IgG4-RD) has resulted in the more frequent identification of IgG4-positivity in submandibular gland inflammations, also uncovering IgG4 overexpression in nonspecific inflammations. These findings lead us to hypothesise that IgG4-positive sialadenitis represents a continuous inflammatory process overlapping histologically with IgG4-RD, possibly differing in aetiology. However, the antigen underlying IgG4 overexpression in IgG4-positive sialadenitis and IgG4-RD remains unknown.Materials and methods Here, we investigated toll-like receptor (TLR) – mediated bacterial inflammation in submandibular gland tissues of patients with IgG4-positive and IgG4-negative chronic inflammatory lesions of the submandibular gland (n = 61), with noninflamed submandibular glands serving as controls (n = 4). Utilising immunohistochemistry, we assessed the expression of TLR2 and TLR4, lipopolysaccharide (LPS) and the P. gingivalis-specific antigen gingipain R1.Results We observed TLR2- and TLR4-immunopositivity in 64 (98%) samples. However, TLR2 and TLR4 staining intensity was significantly stronger in the IgG4-positive group. LPS- and gingipain R1 immunopositivity were observed in 56 (86%) and 58 (89%) samples, respectively. LPS-positivity localised exclusively in mast cell-like cells, while gingipain R1-positivity remained scarce.Conclusions A stronger TLR2 or TLR4 expression in IgG4-positive sialadenitis may indicate a tissue-related factor underlying this form of chronic sialadenitis. LPS- and P. gingivalis immunopositivity remained weak throughout this series. Thus, gram-negative bacteria may not represent pathogens underlying these forms of chronic sialadenitis.
format Article
id doaj-art-9cdc4c584bcb4153be8b13fc2bb9a81d
institution OA Journals
issn 2000-2297
language English
publishDate 2024-12-01
publisher Taylor & Francis Group
record_format Article
series Journal of Oral Microbiology
spelling doaj-art-9cdc4c584bcb4153be8b13fc2bb9a81d2025-08-20T01:53:15ZengTaylor & Francis GroupJournal of Oral Microbiology2000-22972024-12-0116110.1080/20002297.2024.2382633Toll-like receptors 2 and 4, and bacterial proteins in IgG4-related sialadenitis, other types of chronic sialadenitis and sialolithiasisElin Waltimo0Mine Eray1Antti Mäkitie2Caj Haglund3Timo Atula4Jaana Hagström5Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, FinlandDepartment of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandDepartment of Otorhinolaryngology – Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandResearch Programmes Unit, Translational Cancer Medicine, University of Helsinki, Helsinki, FinlandDepartment of Otorhinolaryngology – Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandDepartment of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, FinlandBackground The association of chronic sclerosing sialadenitis and IgG4-related disease (IgG4-RD) has resulted in the more frequent identification of IgG4-positivity in submandibular gland inflammations, also uncovering IgG4 overexpression in nonspecific inflammations. These findings lead us to hypothesise that IgG4-positive sialadenitis represents a continuous inflammatory process overlapping histologically with IgG4-RD, possibly differing in aetiology. However, the antigen underlying IgG4 overexpression in IgG4-positive sialadenitis and IgG4-RD remains unknown.Materials and methods Here, we investigated toll-like receptor (TLR) – mediated bacterial inflammation in submandibular gland tissues of patients with IgG4-positive and IgG4-negative chronic inflammatory lesions of the submandibular gland (n = 61), with noninflamed submandibular glands serving as controls (n = 4). Utilising immunohistochemistry, we assessed the expression of TLR2 and TLR4, lipopolysaccharide (LPS) and the P. gingivalis-specific antigen gingipain R1.Results We observed TLR2- and TLR4-immunopositivity in 64 (98%) samples. However, TLR2 and TLR4 staining intensity was significantly stronger in the IgG4-positive group. LPS- and gingipain R1 immunopositivity were observed in 56 (86%) and 58 (89%) samples, respectively. LPS-positivity localised exclusively in mast cell-like cells, while gingipain R1-positivity remained scarce.Conclusions A stronger TLR2 or TLR4 expression in IgG4-positive sialadenitis may indicate a tissue-related factor underlying this form of chronic sialadenitis. LPS- and P. gingivalis immunopositivity remained weak throughout this series. Thus, gram-negative bacteria may not represent pathogens underlying these forms of chronic sialadenitis.https://www.tandfonline.com/doi/10.1080/20002297.2024.2382633Immunoglobulin G4head and necksalivary glandsubmandibular glandPorphyromonas gingivalislipopolysaccharide
spellingShingle Elin Waltimo
Mine Eray
Antti Mäkitie
Caj Haglund
Timo Atula
Jaana Hagström
Toll-like receptors 2 and 4, and bacterial proteins in IgG4-related sialadenitis, other types of chronic sialadenitis and sialolithiasis
Journal of Oral Microbiology
Immunoglobulin G4
head and neck
salivary gland
submandibular gland
Porphyromonas gingivalis
lipopolysaccharide
title Toll-like receptors 2 and 4, and bacterial proteins in IgG4-related sialadenitis, other types of chronic sialadenitis and sialolithiasis
title_full Toll-like receptors 2 and 4, and bacterial proteins in IgG4-related sialadenitis, other types of chronic sialadenitis and sialolithiasis
title_fullStr Toll-like receptors 2 and 4, and bacterial proteins in IgG4-related sialadenitis, other types of chronic sialadenitis and sialolithiasis
title_full_unstemmed Toll-like receptors 2 and 4, and bacterial proteins in IgG4-related sialadenitis, other types of chronic sialadenitis and sialolithiasis
title_short Toll-like receptors 2 and 4, and bacterial proteins in IgG4-related sialadenitis, other types of chronic sialadenitis and sialolithiasis
title_sort toll like receptors 2 and 4 and bacterial proteins in igg4 related sialadenitis other types of chronic sialadenitis and sialolithiasis
topic Immunoglobulin G4
head and neck
salivary gland
submandibular gland
Porphyromonas gingivalis
lipopolysaccharide
url https://www.tandfonline.com/doi/10.1080/20002297.2024.2382633
work_keys_str_mv AT elinwaltimo tolllikereceptors2and4andbacterialproteinsinigg4relatedsialadenitisothertypesofchronicsialadenitisandsialolithiasis
AT mineeray tolllikereceptors2and4andbacterialproteinsinigg4relatedsialadenitisothertypesofchronicsialadenitisandsialolithiasis
AT anttimakitie tolllikereceptors2and4andbacterialproteinsinigg4relatedsialadenitisothertypesofchronicsialadenitisandsialolithiasis
AT cajhaglund tolllikereceptors2and4andbacterialproteinsinigg4relatedsialadenitisothertypesofchronicsialadenitisandsialolithiasis
AT timoatula tolllikereceptors2and4andbacterialproteinsinigg4relatedsialadenitisothertypesofchronicsialadenitisandsialolithiasis
AT jaanahagstrom tolllikereceptors2and4andbacterialproteinsinigg4relatedsialadenitisothertypesofchronicsialadenitisandsialolithiasis