权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Influenza Attenuates Innate Pulmonary Host Defense against Invasive Pulmonary Aspergillosis

流感削弱肺宿主对侵袭性肺曲霉病的先天防御

基本信息

批准号：
10297248
负责人：
Keven Mara Robinson
金额：
$ 51.06万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-15 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10297248
关键词：
Adhesions Affect Allergic Bronchopulmonary Aspergillosis Alveolar Macrophages Aspergillosis Aspergillus Aspergillus fumigatus Attenuated Bacterial Pneumonia Blood C Type Lectin Receptors CXCL1 gene Cell Adhesion Cells Clinical Critical Illness Data Dendritic Cells Development Disease Effector Cell Exposure to Future Germination Goals Health Hematopoietic Stem Cell Transplantation Host Defense Human Hyphae ITGAX gene Immune Immune response Immune system Immunity Immunocompromised Host Immunology Infection Inflammation Mediators Influenza Influenza A virus Inhalation Inherited Innate Immune System Integration Host Factors Interferons Interleukin-17 Invaded Knowledge Lead Life Lung Lung Transplantation Lung infections Measures Modeling Molecular Morbidity - disease rate Mus Mycoses Natural Immunity Neutropenia Neutrophil Infiltration Organ Pathogenesis Patients Phagocytosis Phenotype Population Predisposition Production Reproduction spores Research Research Project Grants Respiratory Burst Respiratory System Respiratory Tract Infections Risk Risk Factors Role STAT1 gene Scientific Advances and Accomplishments Secondary to Signal Pathway Signal Transduction Structure of parenchyma of lung T-Lymphocyte Therapeutic Intervention Tissue-Specific Gene Expression Work acquired immunodeficiency attenuation base chemokine cytokine fungus in vivo influenza infection insight intravital microscopy macrophage migration mortality neutrophil novel therapeutic intervention pathogen pathogenic fungus patient population prevent receptor recruit respiratory response superinfection trafficking

项目摘要

PROJECT SUMMARY Fungal pathogens are a serious threat to human health. Invasive pulmonary aspergillosis (IPA) is a severe, life- threatening disease that occurs when Aspergillus fumigatus (AF) spores are inhaled into the respiratory tract and invade airway or lung tissue. More than 200,000 cases of invasive aspergillosis occur each year. A newly identified risk factor for IPA in critically ill patients is influenza infection. Influenza is a common respiratory illness that affects 5-20% of the population each year. Our long-term goal is to develop novel therapeutic interventions for use in clinical settings to prevent morbidity and mortality from IPA. The focus of this application is to identify cell signaling pathways that increase susceptibility to invasive fungal disease following influenza infection. Our preliminary data support that preceding influenza inhibits neutrophil recruitment to the lung, in contrast to post- bacterial pneumonia, and neutropenia is a key risk factor for the development of IPA. Additionally, preceding influenza inhibits neutrophil function against secondary AF infection. Furthermore, our preliminary data demonstrate that the pathogen recognition receptor, CD209a, is decreased in post-influenza IPA, suggesting that preceding influenza may inhibit fungal-sensing. Based on our preliminary data, we hypothesize that preceding influenza A infection limits innate immunity and increases susceptibility to invasive pulmonary aspergillosis by inhibiting CD209a and reducing the host response to secondary Aspergillus fumigatus infection in the lung, including neutrophil recruitment and function. Our research aims include 1) Determine whether neutrophil recruitment and effector functions are inhibited in post-influenza IPA, and 2) Determine whether suppression of CD209a-dependent AF sensing promotes post-influenza IPA. The proposed studies will increase our understanding of how influenza inhibits neutrophil migration to and function within the lung in response to subsequent AF infection (Aim1) and how the immune response to AF is initiated in the lung (Aim 2).

项目总结