Formyl-peptide receptor and phagocytosis–How does S. aureus use Formyl-peptide receptor 2 for its own purposes?

甲酰基肽受体是重要的模式识别受体。它们在中性粒细胞和单核细胞上高度表达。它们的激活导致白细胞迁移到感染部位并释放活性氧（ROS）。FPR1感知各种细菌释放的短甲酰化肽，而FPR2被来自金黄色葡萄球菌的酚溶性调节素（PSM）肽激活。由于中性粒细胞属于第一批到达感染病灶的细胞，我们研究了FPRs是否也会影响这些细胞的吞噬能力。我们的初步数据表明，在吞噬过程中，FPR配体和细菌同时刺激中性粒细胞导致被吞噬的金黄色葡萄球菌显著增加。我们观察到这种作用取决于FPR介导的补体受体和FC受体的上调。然而，我们观察到吞噬作用的增加并不一定导致对金黄色葡萄球菌的更好杀灭。因此，我们假设细菌激活FPR1和FPR2导致细菌吞噬能力增加。我们假设只有不能逃离吞噬体的细菌才能被中性粒细胞有效地杀死。我们将阐明FPR2是否也参与了金黄色葡萄球菌的吞噬体逃逸。由于金黄色葡萄球菌也使用psm进行细胞内存活，我们假设金黄色葡萄球菌通过激活FPR2诱导其吞噬。有趣的是，研究表明金黄色葡萄球菌分泌的许多嗜白细胞素仅通过与各种补体或趋化因子受体结合来诱导其毒性潜能。我们想知道，通过FPR激活补体或趋化因子受体的上调或下调是否会导致嗜白细胞素裂解中性粒细胞的能力改变。此外，我们将使用小鼠腹膜炎模型来研究Fpr2的缺失是否会影响各种白细胞素缺乏金黄色葡萄球菌菌株的吞噬作用。

Formyl peptide receptors (FPRs) represent important pattern recognition receptors. They are highly expressed on neutrophils and monocytes. Their activation leads to migration of leukocytes to the infection site and to the release of reactive oxygen species (ROS). FPR1 senses short formylated peptides released by all kinds of bacteria, whereas FPR2 is activated by phenol-soluble modulin (PSM) peptides from Staphylococcus aureus. As neutrophils belong to the first cells reaching the infection focus, we investigated whether FPRs do also influence the phagocytic capacity of these cells. Our preliminary data show that simultaneous stimulation of neutrophils with FPR ligands and bacteria during phagocytosis leads to a significant increase of engulfed S. aureus. We observed that this effect depends on FPR mediated upregulation of complement receptors and of the FC receptor. However, we observed that increased phagocytosis does not necessarily lead to a better killing of S. aureus. Therefore, we hypothesized that activation of FPR1 and FPR2 by bacteria leads to increased phagocytosis of bacteria. We assume that only bacteria that cannot escape from the phagosome can be effectively killed from neutrophils. We will elucidate, if FPR2 is also involved in phagosomal escape of S. aureus. Since S. aureus uses PSMs also for intracellular survival, we suppose that S. aureus induces its phagocytosis willingly via FPR2 activation. Interestingly, it has been shown that many of the secreted leucocidins of S. aureus induce their toxic potential only via binding to various complement or chemokine receptors. We wanted to know, if up- or downregulation of complement or chemokine receptors through FPR activation leads to modified capacity of leucocidins to lyse neutrophils. Furthermore, we will investigate using a mouse peritonitis model, if the loss of Fpr2 influence phagocytosis of a various leucocidin deficient S. aureus strains.