The oral mucosal proteome: perturbation in HIV infection and Candida co infection

口腔粘膜蛋白质组：HIV 感染和念珠菌合并感染的扰动

• 批准号: 7879439
• 负责人: STEPHEN J CHALLACOMBE
• 金额: $ 25.39万
• 依托单位: KING'S COLLEGE LONDON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-17 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7879439
• 关键词: AIDS/HIV problem; Adherence; Affect; Binding; Biochemical; Biological Assay; Biological Phenomena; CCR5 gene; CD209 gene; CXCR4 gene; Candida; Candida albicans; Cells; Data; Dendritic Cells; Epithelial; Epithelial Cells; Epithelium; Etiology; Flow Cytometry; Frequencies; Gene Proteins; Genome; HIV; HIV Infections; HIV Receptors; Human; Immune; Immune response; Immunocompromised Host; Immunoelectron Microscopy; Infection; Investigation; Lasers; Lead; Leukocytes; Liquid substance; Macaca; Mannose; Mediating; Membrane; Modeling; Molecular Profiling; Mouth Diseases; Mucous Membrane; Natural Resistance; Nature; Opportunistic Infections; Oral; Oral Manifestations; Oral candidiasis; Oral cavity; Oral mucous membrane structure; Pathogenesis; Pathway interactions; Patients; Pattern; Physiological; Predisposition; Prevention; Prevention strategy; Process; Property; Protein Secretion; Proteins; Proteome; Proteomics; Quality of life; Research Personnel; Resistance; Reverse Transcriptase Polymerase Chain Reaction; Role; Saliva; Salivary; Sampling; Science; Signal Pathway; Site; Surface; T-Lymphocyte; TLR4 gene; Technology; Time; Tissue Sample; Tissues; Toll-like receptors; Transcript; Transcription Factor AP-1; Vagina; Virus; antimicrobial; base; chemokine; cytokine; effective therapy; functional genomics; health care quality; in vivo; insight; multidisciplinary; novel; oral HIV; oral cavity epithelium; oral infection; oral tissue; pathogen; patient oriented research; programs; protective effect; receptor; receptor expression; reconstitution; response; therapy development; transmission process

DESCRIPTION (provided by applicant): This multidisciplinary application supports a strategy of combining patient-oriented research with the science based investigation of disease causation. The overall aim is to understand the mechanisms that apparently protect the oral epithelium from HIV infection. The long-term objective is to understand the basis of copathogenicity in the immunocompromised host leading to the delivery of more effective therapies. We hypothesize that HIV directly affects the oral epithelial proteome, leading to alterations that promote colonization and infection of the co-pathogen Candida. The specific aims are: 1) To fully characterize the constituents of the oral epithelium that protects the oral mucosa from HIV and Candida infection. Using oral and vaginal epithelial models, and human and macaque samples, the canonical receptors for both HIV and Candida will be investigated by flow cytometry. The epithelial proteome in the presence or absence of HIV and Candida will be then be fully characterized in order to identify protective or susceptibility factors to HIV and Candida infection in these mucosae. Saliva will be applied to the models to investigate the contribution of innate secretory factors present in oral fluids that may inhibit HIV or Candida infection Transcript profiling, quantitative RT-PCR, and Luminex protein assays will be performed to support the proteomic data. 2) To characterize the innate TLR-associated proteomic response elicited by human epithelium during HIV and Candida infection. The HIV- and C. a/b/cans-induced epithelial cytokine, chemokine, TLR1-10 and signaling pathway expression profiles will first be characterized in oral and vaginal epithelial models using proteomics. The PMN-dependent TLR-mediated protection mechanism against oral C. albicans infection will then be fully characterized using transcript profiling, real-time RT-PCR, confocal and immunoelectron microscopy, and siRNAi. Relevance: HIV/AIDS is most commonly transmitted through mucosal membranes. In some circumstances, the oral tissues are exposed to HIV but rarely become infected. Understanding the mechanism by which the oral cavity is apparently protected from infection could lead to the development of therapies to protect other mucosal tissues such as the vagina from infection and transmission of the virus. This could also lead to therapies for the treatment of the co-infections associated with HIV such as oral Thrush.

描述（由申请人提供）：该多学科申请支持将以患者为导向的研究与基于科学的疾病因果关系调查相结合的策略。总体目标是了解明显保护口腔上皮免受艾滋病毒感染的机制。长期目标是了解免疫功能低下宿主的共致病性基础，从而提供更有效的治疗方法。我们假设 HIV 直接影响口腔上皮蛋白质组，导致改变，促进共病原体念珠菌的定植和感染。具体目标是： 1) 全面表征保护口腔粘膜免受艾滋病毒和念珠菌感染的口腔上皮成分。将使用口腔和阴道上皮模型以及人类和猕猴样本，通过流式细胞术研究 HIV 和念珠菌的典型受体。然后将对存在或不存在 HIV 和念珠菌的上皮蛋白质组进行全面表征，以确定这些粘膜中 HIV 和念珠菌感染的保护性或易感性因素。唾液将被应用于模型，以研究口腔液中存在的先天分泌因子对抑制 HIV 或念珠菌感染的贡献。将进行转录谱分析、定量 RT-PCR 和 Luminex 蛋白测定以支持蛋白质组数据。 2) 表征 HIV 和念珠菌感染期间人类上皮引起的先天 TLR 相关蛋白质组学反应。 HIV 和 C. a/b/cans 诱导的上皮细胞因子、趋化因子、TLR1-10 和信号通路表达谱将首先使用蛋白质组学在口腔和阴道上皮模型中进行表征。然后，将使用转录谱分析、实时 RT-PCR、共聚焦和免疫电子显微镜以及 siRNAi 来充分表征 PMN 依赖性 TLR 介导的针对口腔白色念珠菌感染的保护机制。相关性：艾滋病毒/艾滋病最常通过粘膜传播。在某些情况下，口腔组织会暴露于艾滋病毒，但很少被感染。了解口腔明显免受感染的机制可能会导致开发出保护其他粘膜组织（例如阴道）免受病毒感染和传播的疗法。这也可能导致治疗与艾滋病毒相关的合并感染（如鹅口疮）的疗法。

项目成果

Glycosylation of Candida albicans cell wall proteins is critical for induction of innate immune responses and apoptosis of epithelial cells.

• DOI: 10.1371/journal.pone.0050518
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Wagener J;Weindl G;de Groot PW;de Boer AD;Kaesler S;Thavaraj S;Bader O;Mailänder-Sanchez D;Borelli C;Weig M;Biedermann T;Naglik JR;Korting HC;Schaller M
• 通讯作者: Schaller M

Proteins of nucleotide and base excision repair pathways interact in mitochondria to protect from loss of subcutaneous fat, a hallmark of aging.

• DOI: 10.1084/jem.20091834
• 发表时间: 2010-02-15
• 期刊: The Journal of experimental medicine
• 作者: Kamenisch Y;Fousteri M;Knoch J;von Thaler AK;Fehrenbacher B;Kato H;Becker T;Dollé ME;Kuiper R;Majora M;Schaller M;van der Horst GT;van Steeg H;Röcken M;Rapaport D;Krutmann J;Mullenders LH;Berneburg M
• 通讯作者: Berneburg M

Interaction of the mucosal barrier with accessory immune cells during fungal infection.

真菌感染期间粘膜屏障与辅助免疫细胞的相互作用。

• DOI: 10.1016/j.ijmm.2011.04.011
• 发表时间: 2011
• 期刊: International journal of medical microbiology : IJMM
• 作者: Weindl,Gunther;Wagener,Jeanette;Schaller,Martin
• 通讯作者: Schaller,Martin

Activation of MAPK/c-Fos induced responses in oral epithelial cells is specific to Candida albicans and Candida dubliniensis hyphae.

口腔上皮细胞中MAPK/c-FOS诱导反应的激活特异于白色念珠菌和都柏林菌丝菌丝。

• DOI: 10.1007/s00430-011-0209-y
• 发表时间: 2012-02
• 期刊: Medical microbiology and immunology
• 影响因子: 5.4
• 作者: Moyes DL;Murciano C;Runglall M;Kohli A;Islam A;Naglik JR
• 通讯作者: Naglik JR

A peptide derived from the highly conserved protein GAPDH is involved in tissue protection by different antifungal strategies and epithelial immunomodulation.

源自高度保守的蛋白质GAPDH的肽通过不同的抗真菌策略和上皮免疫调节参与组织保护。

• DOI: 10.1038/jid.2012.254
• 发表时间: 2013-01
• 期刊: JOURNAL OF INVESTIGATIVE DERMATOLOGY
• 影响因子: 6.5
• 作者: Wagener, Jeanette;Schneider, Josef J.;Baxmann, Susann;Kalbacher, Hubert;Borelli, Claudia;Nuding, Sabine;Kuechler, Robert;Wehkamp, Jan;Kaeser, Matthias D.;Maiaelander-Sanchez, Daniela;Braunsdorf, Christina;Hube, Bernhard;Schild, Lydia;Forssmann, Wolf-Georg;Korting, Hans-Christian;Liepke, Cornelia;Schaller, Martin
• 通讯作者: Schaller, Martin