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PM exposure and changes in respiratory host defense responses

PM 暴露和呼吸道宿主防御反应的变化

基本信息

批准号：
10320036
负责人：
Neil Alexis
金额：
$ 23.33万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-24 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10320036
关键词：
Acute Address Adverse effects Affect Age Air Pollutants Air Pollution Area Biochemical Bioenergetics Biological Products Biological Response Modifiers Bronchoalveolar Lavage Cell physiology Cells Cessation of life Child China Chinese Chronic Clinical Collaborations Collection Country Data Disease Epidemiology Epithelial Epithelial Cells Equilibrium Exposure to Gene Expression Genomics Glycolysis Health Homeostasis Host Defense Human Human Volunteers Immune Immune System Diseases Immune system Immunologic Markers In Vitro Incidence Individual Infection Inflammation Inflammatory Innate Immune Response Invaded Knowledge Lead Leukocytes Life Link Lung Measures Mediating Mediator of activation protein Medical Metabolism Mitochondria Modeling Modification Mucosal Immune Responses Mucous Membrane Nasal Epithelium Nose Oxidative Phosphorylation Phenotype Predisposition Production Respiration Respiratory Mucosa Respiratory System Respiratory Tract Infections Role Sampling Severities Sputum Structure of mucous membrane of nose Surface System Translational Research Universities air sampling airway immune response antimicrobial arm base cell type defense response epidemiology study experimental study fighting fine particles global health healthy volunteer immune function immune health immunoregulation in vitro testing in vivo innovation macrophage monocyte nasal microbiome novel pathogen pollutant premature recruit respiratory response volunteer

项目摘要

Project Summary It is well established that both acute and chronic exposure to PM significantly affects human health, causing 7 million premature deaths worldwide. It is becoming increasingly evident that PM modifies respiratory host defense responses, which would affect groups of all ages and could have significant implications for children with developing immune systems or susceptible individuals with pre-existing respiratory conditions. The host defense responses of the respiratory tract include innate resident immune cells, such as monocytes/macrophages, and epithelial cells, which provide the first line of defense in the airways against invading pollutants or pathogens. Pollutant-induced modifications of either or both of these components of respiratory host defense will have significant effects on the ability of the host airway to fight infections. While epidemiological studies have demonstrated the association between ambient PM exposure and enhanced susceptibility to infection, a critical knowledge gap exists regarding the mechanistic link between PM-induced immune dysfunction of epithelial cells and airway immune cells and in vivo evidence of respiratory immune health effects. The objective of this proposal is to address how PM modifies cellular mechanisms that are integral to maintaining respiratory immune function homeostasis and link these to observations made in humans in vivo. We hypothesize that PM samples collected during high (vs low) air pollution periods in China will 1) suppress respiratory immune function when tested in vitro (UNC), and 2) show similar deleterious effects when examined in vivo in exposed individuals in China (China collaborators). SA 1 will determine the effects of PM from China on epithelial cell immune and antiviral host defense function and identify the mechanisms mediating these responses. These studies will use our well-established system of differentiated human nasal epithelial cells, which will be exposed to PM collected in China and examined for changes in host defense function and bioenergetic modifications. SA 2 will determine PM-induced modifications of innate immune cell phenotype and functions and the mechanisms mediating these responses. These studies will use sputum and bronchoalveolar lavage macrophages acquired from healthy volunteers, and exposed to PM ex vivo, and examined for changes in immune cell phenotype and function. The role of PM-induced changes in bioenergetics will also be examined. The in vitro studies in SA1 and SA2 will be linked to human in vivo studies proposed in SA3. In SA3, one hundred volunteers from Xinxiang Medical University will be personal air samplers and undergo collection of nasal mucosal samples and induced sputum samples during high and low air pollution periods. Innate immune endpoints as described in SA1 and SA2 will be measured on the collected nasal and sputum samples in SA3.The data derived from these studies will yield important mechanistic information on PM-induced health effects to support current epidemiological associations. Furthermore, these data will address a clinical knowledge gap regarding global health implications for highly polluted and populated countries around the world.

项目总结