Accessory fimbrial subunits and PPAD are necessary for TLR2 activation by Porphyromonas gingivalis.

Autor: Wielento A; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland., Bereta GP; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland., Szczęśniak K; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland., Jacuła A; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland., Terekhova M; Department of Pathology and Immunology, Division of Immunobiology, Washington University School of Medicine, St. Louis, Missouri, USA., Artyomov MN; Department of Pathology and Immunology, Division of Immunobiology, Washington University School of Medicine, St. Louis, Missouri, USA., Hasegawa Y; Department of Microbiology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan., Grabiec AM; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland., Potempa J; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.; Department of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville, Louisville, Kentucky, USA.
Jazyk: angličtina
Zdroj: Molecular oral microbiology [Mol Oral Microbiol] 2023 Aug; Vol. 38 (4), pp. 334-346. Date of Electronic Publication: 2023 Jun 22.
DOI: 10.1111/omi.12427
Abstrakt: Porphyromonas gingivalis is an oral pathogen that promotes dysbiosis by quenching the bactericidal activity of the host immune system while maintaining chronic inflammation, leading to periodontitis. This involves the secretion of virulence factors such as P. gingivalis peptidyl arginine deiminase (PPAD), which converts the C-terminal Arg residues of bacterial and host-derived proteins and peptides into citrulline. We have previously shown that PPAD activity and major fimbriae (containing FimA) are necessary for P. gingivalis to activate Toll-like receptor 2 (TLR2). TLR2 is an important component of the innate immune system and plays a predominant role in the recognition of P. gingivalis by host cells. Here, we extend those findings to show that P. gingivalis strains deficient for PPAD and fimbriae induced almost identical transcriptional profiles in infected primary human gingival fibroblasts (PHGFs), but these differed substantially from the transcriptome elicited by the wild-type ATCC 33277 strain. Apparently, PPAD-modified fimbriae trigger the host cell response to P. gingivalis, as confirmed by showing that the proinflammatory host cell response mediated by TLR2 is dependent on PPAD activity and the presence of fimbriae, with type I fimbriae as the most potent TLR2 activators. We also found that PPAD-modified accessory fimbrial subunits (FimC, FimD, and FimE) alone or in combination are TLR2 ligands in a reporter cell line. Although FimA polymerization to form the fimbrial shaft was not required for TLR2 activation, the secretion and proteolytic maturation of FimA were necessary for signaling by accessory Fim proteins. This was supported by showing that the proinflammatory activation of PHGFs is dependent on PPAD and accessory fimbrial subunits. We conclude that accessory fimbrial subunits are modified by PPAD and stimulate the response to P. gingivalis infection in a TLR2-dependent manner.
(© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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