P.gingivalis interactions with gingival epithelial cells

牙周病是人类最常见的细菌感染之一，对人类造成显著的 医疗保健系统的负担。牙周病的主要病原菌之一是P. 然而，在没有疾病的情况下，牙龈假单胞菌也可以存在于口腔中。互动 牙龈假单胞菌和牙周上皮细胞之间的相互作用对牙周炎的程度有显著影响。 宿主和微生物之间的平衡，以及牙龈的整体健康状况。牙龈假单胞菌可以操纵 上皮细胞信号转导通路，以直接进入宿主细胞并对宿主重新编程 先天免疫力。牙龈假单胞菌的效应分子之一是HAD家族丝氨酸磷酸酶，Serb。 这项建议的目的是确定牙龈假单胞菌和牙龈之间相互作用的结果。 上皮细胞，因为它们与生物体的定植和免疫失调的产生有关。我们会 我们还将继续主要关注多功能的塞族侵袭蛋白和P的调制蛋白的作用。 牙周炎。Cofilin是一种肌动蛋白解聚蛋白，是牙龈假单胞菌侵袭所必需的。我们将研究 塞尔维亚人去磷酸化和失活LIMK激酶的能力将导致cofilin的激活。我们 然后将研究牙龈假单胞菌对ROCK、PAK1和MK2通路的影响，这些通路导致 利姆克。这些相互作用将通过活细胞成像在细胞内观察到。P.牙周炎可以抑制 IL-8的产生部分是通过调节肌动蛋白的动力学来实现的。我们将研究粘附素依赖的肌动蛋白 牙周炎假单胞菌对IL-8的抑制作用牙龈假单胞菌的免疫破坏能力也扩展到 T细胞趋化因子，以及抑制IP-10、ITAC和Mig的机制将被研究。我们还将 开始通过检查T细胞对感染的上皮细胞的反应来评估生物学相关性 和牙龈假单胞菌。这些研究将为宿主信号的靶向提供详细的分子分析 牙龈假单胞菌的转导以及特定效应磷酸酶的作用。归根结底， 所获得的知识可以发展成可用于干预P的策略。 牙龈上皮细胞相互作用，以确保结果是对宿主无害的。 相关性(请参阅说明)： 牙龈假单胞菌是困扰数百万美国人的牙周病的原因之一。在这项研究中，我们将 检查牙龈假单胞菌与被该生物定植的人类细胞之间的相互作用。这个 要收集的信息可以用来确定新型治疗剂的目标，旨在 干扰牙龈假单胞菌的定植和生存策略。

Periodontal diseases are one of the most common bacterial infections of humans and impose a significant burden on the health care system. One of the predominant pathogens in periodontal disease is P. gingivalis; however, P. gingivalis can also inhabit the oral cavity in the absence of disease. The interaction between P. gingivalis and gingival epithelial cells makes a significant contribution to the degree of equilibrium between host and microbe, and to overall gingival health status. P. gingivalis can manipulate epithelial cell signal transduction pathways in order to direct entry into the host cell and to reprogram host innate immunity. One of the effector molecules of P. gingivalis is the HAD family serine phosphatase, SerB. The goal of this proposal is define the outcomes of the interaction between P. gingivalis and gingival epithelial cells as they relate colonization of the organism and the generation of immune dysbiosis. We shall also continue our major focus on the role of the functionally versatile SerB invasin and modulin of P. gingivalis. Cofilin, an actin depolymerizing protein, is required for P. gingivalis invasion. We will examine the ability of SerB to dephosphorylate and inactivate LIMK kinase which will lead to activation of cofilin. We will then investigate the impact of P. gingivalis on ROCK, PAK1 and MK2 pathways that lead to activation of LIMK. These interactions will be observed within the cell by live cell imaging. P..gingivalis can suppress IL-8 production in part through regulation of actin dynamics. We shall study the cofilin dependent, actin mediated suppression of IL-8 by P. gingivalis. The immune disruptive ability of P. gingivalis also extends to T-cell chemokines, and the mechanism of suppression of IP-10, ITAC and Mig will be studied. We will also begin to assess biological relevance by examining T-cell migration in response to epithelial cells infected with P. gingivalis. These studies will provide a detailed molecular analysis of the targeting of host signal transduction by P. gingivalis along with the role of a specific effector phosphatase. Ultimately, the knowledge gained could be developed into strategies that could be utilized to intervene in the P. gingivalis-epithelial cell interaction to ensure that the outcome is non-harmful to the host. RELEVANCE (See instructions): P. gingivalis is a cause of periodontal diseases that afflict millions of Americans. In this study we will examine the interactions between P. gingivalis and the human cells that are colonized by the organism. The information to be gathered could be used to identify targets for novel therapeutic agents designed to interfere with the colonization and survival strategies of P. gingivalis.