Skin barrier function and the microbiome

皮肤屏障功能和微生物组

• 批准号: 8858115
• 负责人: Richard L Gallo
• 金额: $ 18.83万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8858115
• 关键词: Atopic Dermatitis; Aureolysin; Bacteria; Basement membrane; Biological Process; Camping; Cell Degranulation; Cells; Communication; Cutaneous; Data; Defect; Dermal; Dermis; Development; Elements; Epidermis; Epithelial; Equilibrium; Event; Functional disorder; Gene Expression Profile; Gene Silencing; Goals; Human; Immune; Immune response; Immune system; Immunity; Infection; Inflammation; Kidney; Laboratories; Life; Lung; Measures; Microbe; Molecular; Mus; Myelogenous; Organ; Peptide Hydrolases; Peptides; Positioning Attribute; Protease Inhibitor; RNA Sequences; Regulation; Resistance; Role; Serine Protease; Serine Proteinase Inhibitors; Skin; Small Interfering RNA; Staphylococcus aureus; Stratum corneum; Structure; Surface; TNF receptor-associated factor 1; Testing; Time; Toxin; Work; antimicrobial peptide; cathelicidin; cell type; commensal microbes; extracellular; fighting; glutamyl endopeptidase; keratinocyte; mast cell; microbial; microbial community; microbiome; mutant; novel; pathogen; pathogenic bacteria; public health relevance; response; skin disorder; transcriptome sequencing

 DESCRIPTION (provided by applicant): The surface commensal microbial community has been shown to influence the function and development of the immune system, thus potentially participating in the pathophysiology of several important diseases of the skin, gut, kidney and lung. With increased appreciation that normal microbial communities exist in equilibrium with, and in many cases benefit the host, recent work has sought to better understand the mechanisms by which we permit survival of our skin commensal microbiome and how the microbiome controls mammalian immune responses. We have discovered that it was wrong to assume that bacteria are normally totally separated from us by the epidermis. Strong evidence now shows that microbial communities are in an equilibrium across the basement membrane zone and populate the dermal stroma of normal skin. These observations show that the surface microbiome can get into the position in direct priming with live cells below the epithelial surface therefore influencing cutaneous immunity. Importantly, the observation that microbes enter the dermis is not evidence for infection, rather this findings show that products made by microbes are communicating with various cell types existing in the dermis. The overall goal of this proposal is to understand mechanisms how microbes breakthrough epidermal barrier to enter the dermis, explore the elements of the skin innate immune barrier that regulate microbial entry into the dermis, and begin to test the hypothesis that microbial entry is a rate-limiting step of induction of immunological responses by skin microbiome. Our aims are as follows: Aim 1: Understand how bacteria break through the skin barrier to enter the dermis. Aim 2: Understand how innate immune barriers control entry of commensal and pathogenic bacteria Aim 3: Determine if the entry of bacteria into the dermis results in an immunological responses. Successful completion of these aims will provide new information regarding control of an important and novel aspect of the functional interaction between microbiome and cutaneous immunity in homeostatic or pathogenic aspects.

 描述（由应用提供）：表面共同微生物群落已显示出影响免疫系统的功能和发育，因此有可能参与皮肤，肠，肾脏和肺的几种重要疾病的病理生理学。随着人们对正常微生物群落的平衡存在与宿主有益的均衡，最近的工作已经解决了我们允许我们允许皮肤生存相关微生物组生存的机制，以及微生物组如何控制哺乳动物的免疫增长。我们发现，假设细菌通常与表皮完全分离是错误的。现在，有力的证据表明，微生物群落位于基底膜区域的等效物中，并填充了正常皮肤的皮肤基质。这些观察结果表明，表面微生物组可以在直接启动的位置，而在上皮表面以下的活细胞会影响切割可用的免疫力。重要的是，关于微生物进入真皮的观察不是感染的证据，而是这一发现表明，微生物制造的产品正在与真皮中存在的各种细胞类型进行通信。该提案的总体目标是了解微生物如何突破表皮屏障进入真皮，探索皮肤先天免疫屏障的元素，从而调节微生物进入真皮的微生物，并开始测试微生物进入的假设是，微生物进入是通过肤色微生物诱导免疫学反应的速率限制步骤。我们的目标如下：目标1：了解细菌如何穿透皮肤屏障进入真皮。目标2：了解先天免疫障碍如何控制共生和致病细菌的进入目标3：确定细菌进入真皮是否会导致免疫反应。这些目标的成功完成将提供有关控制微生物组和皮肤免疫学之间功能相互作用的重要和新颖方面的新信息。