TLR2 Activation by Porphyromonas gingivalis Requires Both PPAD Activity and Fimbriae.

Wielento, Aleksandra; Bereta, Grzegorz P; Łagosz-Ćwik, Katarzyna B; Eick, Sigrun; Lamont, Richard J; Grabiec, Aleksander M; Potempa, Jan (2022). TLR2 Activation by Porphyromonas gingivalis Requires Both PPAD Activity and Fimbriae. Frontiers in immunology, 13, p. 823685. Frontiers Research Foundation 10.3389/fimmu.2022.823685

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Porphyromonas gingivalis, a keystone oral pathogen implicated in development and progression of periodontitis, may also contribute to the pathogenicity of diseases such as arthritis, atherosclerosis, and Alzheimer's. P. gingivalis is a master manipulator of host immune responses due to production of a large variety of virulence factors. Among these, P. gingivalis peptidilarginine deiminase (PPAD), an enzyme unique to P. gingivalis, converts C-terminal Arg residues in bacterium- and host-derived proteins and peptides into citrulline. PPAD contributes to stimulation of proinflammatory responses in host cells and is essential for activation of the prostaglandin E2 (PGE2) synthesis pathway in gingival fibroblasts. Since P. gingivalis is recognized mainly by Toll-like receptor-2 (TLR2), we investigated the effects of PPAD activity on TLR2-dependent host cell responses to P. gingivalis, as well as to outer membrane vesicles (OMVs) and fimbriae produced by this organism. Using reporter cell lines, we found that PPAD activity was required for TLR2 activation by P. gingivalis cells and OMVs. We also found that fimbriae, an established TLR2 ligand, from wild-type ATCC 33277 (but not from its isogenic PPAD mutant) enhanced the proinflammatory responses of host cells. Furthermore, only fimbriae from wild-type ATCC 33277, but not from the PPAD-deficient strains, induced cytokine production and stimulated expression of genes within the PGE2 synthesis pathway in human gingival fibroblasts via activation of the NF-ĸB and MAP kinase-dependent signaling pathways. Analysis of ten clinical isolates revealed that type I FimA is preferable for TLR2 signaling enhancement. In conclusion, the data strongly suggest that both PPAD activity and fimbriae are important for TLR2-dependent cell responses to P. gingivalis infection.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > School of Dental Medicine > Department of Periodontology
04 Faculty of Medicine > School of Dental Medicine > Periodontics Research

UniBE Contributor:

Eick, Sigrun

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1664-3224

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Pubmed Import

Date Deposited:

19 Apr 2022 13:27

Last Modified:

24 Apr 2022 02:00

Publisher DOI:

10.3389/fimmu.2022.823685

PubMed ID:

35432342

Uncontrolled Keywords:

Porphyromonas gingivalis TLR2 citrullination fimbriae gingival fibroblasts inflammation peptidylarginine deiminase reporter cell lines

BORIS DOI:

10.48350/169352

URI:

https://boris.unibe.ch/id/eprint/169352

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