特发性肺纤维化
医学
免疫系统
免疫学
肺
纤维化
肺炎
肺纤维化
囊性纤维化
巨噬细胞
吞噬作用
中性粒细胞弹性蛋白酶
先天免疫系统
炎症
病理
内科学
生物
体外
生物化学
作者
Helen Warheit-Niemi,Summer J. Edwards,Shuvasree SenGupta,Carole A. Parent,Xiaofeng Zhou,David N. O’Dwyer,Bethany B. Moore
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2022-02-22
卷期号:7 (4)
被引量:8
标识
DOI:10.1172/jci.insight.152690
摘要
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by collagen deposition within the lung interstitium. Bacterial infection is associated with increased morbidity and more rapid mortality in IPF patient populations, and pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) are commonly isolated from the lungs of hospitalized patients with IPF. Despite this, the effects of fibrotic lung injury on critical immune responses to infection remain unknown. In the present study, we show that, like humans with IPF, fibrotic mice infected with MRSA exhibit increased morbidity and mortality compared with uninfected fibrotic mice. We determine that fibrosis conferred a defect in MRSA clearance compared with nonfibrotic mice, resulting from blunted innate immune responses. We show that fibrosis inhibited neutrophil intracellular killing of MRSA through impaired neutrophil elastase release and oxidative radical production. Additionally, we demonstrate that lung macrophages from fibrotic mice have impaired phagocytosis of MRSA. Our study describes potentially novel impairments of antimicrobial responses upon pulmonary fibrosis development, and our findings suggest a possible mechanism for why patients with IPF are at greater risk of morbidity and mortality related to infection.
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