Lysosomal maturation during periodontal infections

描述（由申请人提供）：牙周炎是一种慢性炎症性疾病，由红色复合牙周病原体引起的多微生物感染引起，其中最具特征的是牙龈卟啉卟啉菌（p.g.）。为了在敌对宿主环境中建立慢性感染，病原体设计了一些机制，通过这些机制，它们可以逃避或破坏宿主旨在消除它们的防御机制，其中一种机制是溶酶体介导的降解。我们提出牙龈卟啉卟啉菌通过劫持自噬体途径来破坏吞噬酶体的降解，从而在巨噬细胞中产生保护性的细胞内生态位。具体来说，我们将验证自噬体形成的上调对于牙龈假单胞菌在巨噬细胞中的存活至关重要，并且需要MREG介导的溶酶体成熟的假设。在具体的目标1中，我们将测试p.g.隔离到自噬体中并保护其免受溶酶体降解的假设。在具体目标2中，我们关注p.g.进入巨噬细胞的模式如何有助于其运输概况和持久性。具体目标3

DESCRIPTION (provided by applicant): Periodontitis is a chronic inflammatory disease that is driven by polymicrobial infection by red-complex periodontal pathogens, the best characterized of which is P. gingivalis (P.g.). To establish chronic infection in hostile host environments pathogens devise mechanisms by which they evade or subvert host defense mechanisms designed to eliminate them, one such mechanism is lysosome mediated degradation. We propose that P. gingivalis subverts phagolysosome degradation by hijacking the autophagosomal pathway to create a protective intracellular niche in macrophages. Specifically, we will test the hypothesis that upregulation of autophagosome formation is critical for P. gingivalis survival in macrophages and requires MREG mediated lysosomal maturation. In specific aim 1 we will test the hypothesis that P. g. sequesters into autophagosomes and confers protection from lysosomal degradation. In specific aim 2 we focus on how the mode of P. g. entry into macrophages contributes to its trafficking profile and persistence. Specific aim 3 will focus on the LPS-TLR mediated signaling pathways contributing to lysosome maturation as it relates to autophagy.