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Karger AG","issue":"2","license":[{"start":{"date-parts":[[2015,11,28]],"date-time":"2015-11-28T00:00:00Z","timestamp":1448668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2015,11,28]],"date-time":"2015-11-28T00:00:00Z","timestamp":1448668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Innate Immun"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p>Aspiration pneumonia is a life-threatening infectious disease often caused by oral anaerobic and periodontal pathogens such as &lt;i&gt;Porphyromonas gingivalis.&lt;\/i&gt; This organism produces proteolytic enzymes, known as gingipains, which manipulate innate immune responses and promote chronic inflammation. Here, we challenged mice with &lt;i&gt;P. gingivalis&lt;\/i&gt; W83 and examined the role of gingipains in bronchopneumonia, lung abscess formation, and inflammatory responses. Although gingipains were not required for &lt;i&gt;P. gingivalis&lt;\/i&gt; colonization and survival in the lungs, they were essential for manifestation of clinical symptoms and infection-related mortality. Pathologies caused by wild-type (WT) &lt;i&gt;P. gingivalis&lt;\/i&gt; 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 &lt;i&gt;P. gingivalis-&lt;\/i&gt;related morbidity and mortality than lysine-specific gingipains. Thus, inhibition of gingipain may be a useful adjunct treatment for &lt;i&gt;P. gingivalis-&lt;\/i&gt;mediated aspiration pneumonia.<\/jats:p>","DOI":"10.1159\/000441724","type":"journal-article","created":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T17:01:12Z","timestamp":1448643672000},"page":"185-198","source":"Crossref","is-referenced-by-count":89,"title":["Gingipains: Critical Factors in the Development of Aspiration Pneumonia Caused by &lt;b&gt;&lt;i&gt;Porphyromonas gingivalis&lt;\/i&gt;&lt;\/b&gt;"],"prefix":"10.1159","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5432-8739","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Benedyk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr 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