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PLoS Pathog:新发现!可抵御肺部霉菌感染的新型关键分子

来源:生物谷 2015-02-10 10:03

2015年2月10日 讯 /生物谷BIOON/ --近日,发表在国际杂志PLoS Pathogens上的一篇研究报告中,来自蒙大拿州立大学(Montana State University)的研究人员通过研究发现一种名为IL-1α的关键分子或可帮助抵御肺部感染,有效改善患者的机体健康。

Alayna Caffrey博士表示,我们主要研究人类机体对烟曲霉菌的早期免疫反应,烟曲霉菌是一种在土壤或堆肥中生存的常见霉菌,其可以使得抵抗力较低的个体引发严重的肺部感染,比如白血病患者、化疗患者或器官移植患者。烟曲霉菌引发的死亡率在不同的人群中为30%至90%。

为了降低免疫系统减弱患者烟曲霉菌的感染率,研究人员通过对健康的免疫系统进行研究来观察其对烟曲霉菌产生免疫反应的机制,研究者发现了一种名为IL-1α的新型分子可以促进白细胞进入到感染位点实施真菌的杀灭活动;如果没有得到合适的白细胞补给,烟曲霉菌就会继续入侵肺部组织并且不断生长,直至引发患者死亡。

最后研究者指出,后期我们还会通过更为深入的研究来调查IL-1α分子所扮演的角色,我们希望通过后期的研究将以IL-1α分子为基础开发出更多有效抵御烟曲霉菌感染的新型疗法,从而为改善免疫力较低个体/患者的生活质量带来帮助。(生物谷Bioon.com)

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IL-1α Signaling Is Critical for Leukocyte Recruitment after Pulmonary Aspergillus fumigatus Challenge.

Caffrey AK1, Lehmann MM1, Zickovich JM1, Espinosa V2, Shepardson KM3, Watschke CP1, Hilmer KM1, Thammahong A3, Barker BM4, Rivera A2, Cramer RA3, Obar JJ1.

Aspergillus fumigatus is a mold that causes severe pulmonary infections. Our knowledge of how A. fumigatus growth is controlled in the respiratory tract is developing, but still limited. Alveolar macrophages, lung resident macrophages, and airway epithelial cells constitute the first lines of defense against inhaled A. fumigatus conidia. Subsequently, neutrophils and inflammatory CCR2+ monocytes are recruited to the respiratory tract to prevent fungal growth. However, the mechanism of neutrophil and macrophage recruitment to the respiratory tract after A. fumigatus exposure remains an area of ongoing investigation. Here we show that A. fumigatus pulmonary challenge induces expression of the inflammasome-dependent cytokines IL-1β and IL-18 within the first 12 hours, while IL-1α expression continually increases over at least the first 48 hours. Strikingly, Il1r1-deficient mice are highly susceptible to pulmonary A. fumigatus challenge exemplified by robust fungal proliferation in the lung parenchyma. Enhanced susceptibility of Il1r1-deficient mice correlated with defects in leukocyte recruitment and anti-fungal activity. Importantly, IL-1α rather than IL-1β was crucial for optimal leukocyte recruitment. IL-1α signaling enhanced the production of CXCL1. Moreover, CCR2+ monocytes are required for optimal early IL-1α and CXCL1 expression in the lungs, as selective depletion of these cells resulted in their diminished expression, which in turn regulated the early accumulation of neutrophils in the lung after A. fumigatus challenge. Enhancement of pulmonary neutrophil recruitment and anti-fungal activity by CXCL1 treatment could limit fungal growth in the absence of IL-1α signaling. In contrast to the role of IL-1α in neutrophil recruitment, the inflammasome and IL-1β were only essential for optimal activation of anti-fungal activity of macrophages. As such, Pycard-deficient mice are mildly susceptible to A. fumigatus infection. Taken together, our data reveal central, non-redundant roles for IL-1α and IL-1β in controlling A. fumigatus infection in the murine lung.

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