Neutrophil migration from blood to tissue-residing microbes is governed by a series of chemoattractant gradients of both endogenous and microbial origin. Periodontal disease is characterized by neutrophil accumulation in the gingival pocket, recruited by the subgingival biofilm consisting mainly of gram-negative, anaerobic and proteolytic species such as Porphyromonas gingivalis. The fact that neutrophils are the dominating cell type in the gingival pocket suggests that neutrophil-specific chemoattractants are released by subgingival bacteria, but characterization of chemoattractants released by subgingival biofilm species remains incomplete. In the present study we characterized small (< 3 kDa) soluble chemoattractants released by growing P. gingivalis, and show that these are selective for neutrophils. Most neutrophil chemoattractant receptors are expressed also by mononuclear phagocytes, the free fatty acid receptor 2 (FFAR2) being an exception. In agreement with the selective neutrophil recruitment, the chemotactic activity found in P. gingivalis supernatants was mediated in part by a mixture of short chain fatty acids (SCFAs) that are recognized by FFAR2, and other leukocytes (including monocytes) did not respond to SCFA stimulation. Although SCFAs, produced by bacterial fermentation of dietary fiber in the gut, has previously been shown to utilize FFAR2, our data demonstrate that the pronounced proteolytic metabolism employed by P. gingivalis (and likely also other subgingival biofilm bacteria associated with periodontal diseases) may result in the generation of SCFAs that attract neutrophils to the gingival pocket. This finding highlights the interaction between SCFAs and FFAR2 in the context of P. gingivalis colonization during periodontal disease, but may also have implications for other inflammatory pathologies involving proteolytic bacteria.

中性粒细胞从血液迁移到组织中的微生物受到一系列内源性和微生物来源的趋化剂梯度的控制。牙周病的特征是牙龈袋中中性粒细胞积聚，由主要由革兰氏阴性菌、厌氧菌和蛋白水解菌（例如牙龈卟啉单胞菌）组成的龈下生物膜募集。中性粒细胞是龈袋中的主要细胞类型这一事实表明，中性粒细胞特异性化学引诱剂是由龈下细菌释放的，但对龈下生物膜物种释放的化学引诱剂的表征仍然不完整。在本研究中，我们表征了生长中的牙龈卟啉单胞菌释放的小（< 3 kDa）可溶性化学引诱剂，并表明它们对中性粒细胞具有选择性。大多数中性粒细胞趋化受体也由单核吞噬细胞表达，游离脂肪酸受体 2 (FFAR2) 是一个例外。与选择性中性粒细胞募集一致，牙龈卟啉单胞菌上清液中发现的趋化活性部分是由 FFAR2 识别的短链脂肪酸 (SCFA) 混合物介导的，而其他白细胞（包括单核细胞）对 SCFA 没有反应刺激。尽管肠道中膳食纤维细菌发酵产生的短链脂肪酸 SCFA 先前已被证明可以利用 FFAR2，但我们的数据表明，牙龈卟啉单胞菌（以及可能还有与牙周病相关的其他龈下生物膜细菌）所采用的显着蛋白水解代谢可能会导致产生 SCFA，将中性粒细胞吸引至牙龈袋。这一发现强调了 SCFA 和 FFAR2 在 P. 背景下的相互作用。 牙龈炎在牙周病期间定植，但也可能对涉及蛋白水解细菌的其他炎症病理产生影响。