Gingipains: Critical Factors in the Development of Aspiration Pneumonia Caused by Porphyromonas gingivalis
Open accessAbstract
Aspiration pneumonia is a life-threatening infectious disease often caused by oral anaerobic and periodontal pathogens such as Porphyromonas gingivalis. This organism produces proteolytic enzymes, known as gingipains, which manipulate innate immune responses and promote chronic inflammation. Here, we challenged mice with P. gingivalis W83 and examined the role of gingipains in bronchopneumonia, lung abscess formation, and inflammatory responses. Although gingipains were not required for P. gingivalis colonization and survival in the lungs, they were essential for manifestation of clinical symptoms and infection-related mortality. Pathologies caused by wild-type (WT) P. gingivalis W83, including hemorrhage, necrosis, and neutrophil infiltration, were absent from lungs infected with gingipain-null isogenic strains or WT bacteria preincubated with gingipain-specific inhibitors. Damage to lung tissue correlated with systemic inflammatory responses, as manifested by elevated levels of TNF, IL-6, IL-17, and C-reactive protein. These effects were unequivocally dependent on gingipain activity. Gingipain activity was also implicated in the observed increase in IL-17 in lung tissues. Furthermore, gingipains increased platelet counts in the blood and activated platelets in the lungs. Arginine-specific gingipains made a greater contribution to P. gingivalis-related morbidity and mortality than lysine-specific gingipains. Thus, inhibition of gingipain may be a useful adjunct treatment for P. gingivalis-mediated aspiration pneumonia.
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P. gingivalis can produce Gingipain, which affects the innate immune response and promotes chronic inflammation.
“Animal experiments (Benedyk et al., 2016) suggested that P. gingivalis can produce Gingipain, which then affect the innate immune response and promote chronic inflammation.”
From Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection (2020) · cites this paper as Benedyk et al., 2016
After infection with P. gingivalis, pathological manifestations such as intrapulmonary hemorrhage, necrosis, and neutrophil infiltration occur.
“Pathological manifestations such as intrapulmonary hemorrhage, necrosis, and neutrophil infiltration occur after infection with P. gingivalis.”
From Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection (2020) · cites this paper as Benedyk et al., 2016
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Research works printed but not linked: 2
- [41]Terpenning MS Taylor GW Lopatin DE Kerr CK Dominguez BL Loesche WJ 2001 Aspiration pneumonia: dental and oral risk factors in an older veteran population J Am Geriatr Soc 49 557 563 11380747
- [42]Kadowaki T Baba A Abe N Takii R Hashimoto M 2004 Suppression of pathogenicity of Porphyromonas gingivalis by newly developed gingipain inhibitors Mol Pharmacol 66 1599 1606 15361547
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- Authors
- Benedyk, M., Mydel, P. M., Delaleu, N., Płaza, K., Gawron, K., Milewska, A., Maresz, K., Koziel, J., Pyrc, K., & Potempa, J.
- Affiliations
- Jagiellonian University (PL)
- University of Bergen (NO)
- ORCID
- Venue
- Journal of Innate Immunity
- Publisher
- S. Karger AG
- Published
- 2015-11-28
- Volume
- 8
- Issue
- 2
- Pages
- 185-198
- ISSN
- 1662-811X (ISSN-L)
- 1662-8128
- PMC
- PMC4801669
- OpenAlex
- W2287343686
- Cited by
- 98
- References
- 76
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 7 · 2023: 4 · 2022: 10 · 2021: 15 · 2020: 14 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 5
- FWCI
- 7.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Innate Immunity (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion, cc-by-nc-nd)
- Funders
- European Commission
- National Institute of Dental and Craniofacial Research (DE 022597, R01DE022597, R01DE009761, DE09761)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Immunology and Microbiology › Microbiology › Microbial infections and disease research
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Keywords
- gingipains, Porphyromonas gingivalis, aspiration pneumonia, IL-17, systemic inflammation, platelet activation, lung abscess, bronchopneumonia, periodontal pathogens, innate immune evasion
- MeSH terms
- Gingipain Cysteine Endopeptidases, Animals, Blood Platelets, Cysteine Endopeptidases, Female, Hemorrhage, Mice, Inbred BALB C, Necrosis, Neutrophils, Platelet Count, Pneumonia, Aspiration, Platelet Activation, Cytokines, Bacteroidaceae Infections, Porphyromonas gingivalis, Adhesins, Bacterial, Neutrophil Infiltration, Mice
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