Pneumonia Biology

肺炎生物学

• 批准号: 10543425
• 负责人: JOSEPH P MIZGERD
• 金额: $ 83.88万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-11 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10543425
• 关键词: Acceleration; Acute; Address; Adult; Affect; Age; Aging; Alveolar Macrophages; Award; Bacteria; Biology; Cardiovascular Diseases; Child; Chronic Disease; Chronic lung disease; Coupled; Defense Mechanisms; Development; Disease; Elderly; Epithelial Cells; Grant; Hospitalization; Immune response; Incidence; Individual; Lung; Lung diseases; Lung infections; Mediating; Microbe; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Natural Immunity; Organism; Pneumonia; Predisposition; Productivity; Pulmonary Inflammation; Research; Role; Virulence; Virus; acute infection; adaptive immunity; burden of illness; lung failure; microbial; middle age; mortality; mortality risk; novel strategies; pathobiont; prevent; programs; respiratory

Abstract Pneumonia biology should be the focus of an R35 from the NHLBI. Pneumonia is a leading global burden of disease in every analysis. It kills more children worldwide and hospitalizes more US children than does any other disease. Older adults are even more affected. The incidence and risk of death from pneumonia increase throughout adulthood until becoming orders of magnitude greater than for young children. But the idea that adults have to be old and frail to get pneumonia is a counter-productive misconception. Pneumonia susceptibility is pronounced in middle age, with the median age of non-immunocompromised US adults hospitalized for pneumonia being 57 years. In addition to the directly attributable immediate morbidity and mortality, pneumonia also accelerates unhealthy aging, including exacerbations and more rapid decline of chronic pulmonary diseases, cardiovascular diseases, and more. A wide ranging assortment of viruses, bacteria, and other microbes causes pneumonia, with no one organism responsible for as much as a tenth of cases. It is not about the microbe. These are pathobionts, not pathogens. They circulate among us repeatedly or live on us continuously, growing in the lung to cause pneumonia only under exceptional circumstances. Whether pneumonia ensues depends on the quality and quantity of the host response. Pneumonia results from failures of lung defense more than from microbial virulence. We need to understand the lung defenses that normally prevent pneumonia in young healthy adults before we can identify, prevent, or reverse what goes wrong to make individuals susceptible to pneumonia. Our ongoing research program is addressing the question of lung defense against pneumonia with a long-standing and continuing focus on pulmonary inflammation and innate immunity that is now coupled with a newer emphasis on naturally acquired heterotypic adaptive immunity against respiratory pathobionts. This research program includes 2 ongoing NHLBI R01s that are defining roles of lung epithelial cells and alveolar macrophages in mediating protection against pneumonia. These 2 grants together total 26 R01-years of support from the NHLBI, and we propose unifying these distinct components of our mature and productive research program into a more integrated R35 award. During the coming years, we envision our research program (i) advancing mechanistic understanding of lung defense against pneumonia by functionally integrating the activities of lung constituents and adaptive immunity, (ii) leveraging discoveries in lung defense to generate new approaches to preventing and curing pneumonia, and (iii) forwarding the concept that pneumonia susceptibility is a chronic disease of aging, and attacking the mechanisms of susceptibility rather than (or in addition to) the acute infection has the greatest promise for diminishing the burden of this lung disease.

摘要 肺炎生物学应该是NHLBI R35的重点。肺炎是一种主要的全球负担， 疾病在每一个分析。它杀死了世界上更多的儿童，使更多的美国儿童住院治疗， 其他疾病。老年人受到的影响更大。肺炎的发病率和死亡风险增加 在整个成年期，直到变得比幼儿大几个数量级。但是要说 成年人必须年老体弱才能感染肺炎是一种适得其反的误解。肺炎 易感性在中年明显，非免疫功能低下的美国成年人的中位年龄 因肺炎住院57年。除了可直接归因的直接发病率和 死亡率，肺炎也加速了不健康的老龄化，包括恶化和更快的下降， 慢性肺部疾病、心血管疾病等等。各种各样的病毒， 细菌和其他微生物引起肺炎，没有一种有机体负责多达十分之一的肺炎。 例这与微生物无关。这些是致病菌，不是病原体。它们在我们中间流通 反复或不断地活在我们身上，只有在特殊情况下才能在肺部生长引起肺炎 情节肺炎是否能扩大取决于宿主反应的质量和数量。 肺炎更多地是由于肺部防御功能的丧失而不是微生物的毒力。我们需要了解 在我们能够识别、预防或治疗肺炎之前， 逆转使人易患肺炎的错误。我们正在进行的研究项目是 解决肺部防御肺炎的问题，长期持续关注 肺部炎症和先天免疫现在与对自然获得性免疫的新强调相结合 针对呼吸道致病菌的异型适应性免疫。该研究项目包括2个正在进行的 NHLBI R01是肺上皮细胞和肺泡巨噬细胞在介导保护中的定义作用 对抗肺炎这两项赠款总共为NHLBI提供了26 R01年的支持，我们建议 将我们成熟和富有成效的研究计划的这些不同组成部分统一到一个更集成的R35中 奖在未来的几年里，我们设想我们的研究计划（i）推进机械理解 肺防御肺炎功能整合活动的肺成分和适应性 免疫力，（ii）利用肺防御的发现来产生预防和治疗的新方法 （iii）提出肺炎易感性是一种慢性衰老疾病的概念， 攻击易感性机制而不是（或除了）急性感染具有最大的 承诺减轻这种肺病的负担。

项目成果

CPHEN-011: Comprehensive phenotyping of murine lung resident lymphocytes after recovery from pneumococcal pneumonia.

CPHEN-011：肺炎球菌肺炎恢复后小鼠肺驻留淋巴细胞的综合表型。

• DOI: 10.1002/cyto.a.24522
• 发表时间: 2022-11
• 期刊: Cytometry. Part A : the journal of the International Society for Analytical Cytology

SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19.

• DOI: 10.1093/jnen/nlac056
• 发表时间: 2022-08-16
• 期刊: Journal of neuropathology and experimental neurology
• 影响因子: 3.2

Inflammation and Pneumonia: Why Are Some More Susceptible than Others?

炎症和肺炎：为什么有些比其他人更容易受到影响？

• DOI: 10.1016/j.ccm.2018.07.002
• 发表时间: 2018-12
• 期刊: Clinics in chest medicine
• 影响因子: 5.7
• 作者: Mizgerd JP

Expression of Piwi protein MIWI2 defines a distinct population of multiciliated cells.

Piwi 蛋白 MIWI2 的表达定义了一个独特的多纤毛细胞群。

• DOI: 10.1172/jci94639
• 发表时间: 2017
• 期刊: The Journal of clinical investigation
• 作者: Wasserman,GregoryA;Szymaniak,AleksanderD;Hinds,AnneC;Yamamoto,Kazuko;Kamata,Hirofumi;Smith,NicoleMs;Hilliard,KristieL;Carrieri,Claudia;Labadorf,AdamT;Quinton,LeeJ;Ai,Xingbin;Varelas,Xaralabos;Chen,Felicia;Mizgerd,JosephP
• 通讯作者: Mizgerd,JosephP

Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury.

• DOI: 10.1172/jci.insight.149955
• 发表时间: 2022-12-08
• 期刊: JCI INSIGHT
• 影响因子: 8
• 作者: Korkmaz, Filiz T.;Shenoy, Anukul T.;Symer, Elise M.;Baird, Lillia A.;Odom, Christine V.;Arafa, Emad I.;Na, Elim;Dimbo, Ernest L.;Molina-Arocho, William;Brudner, Matthew;Standiford, Theodore J.;Mehta, Jawahar L.;Sawamura, Tatsuya;Jones, Matthew R.;Mizgerd, Joseph P.;Traber, Katrina E.;Quinton, Lee J.
• 通讯作者: Quinton, Lee J.