Laboratory of Immunobiology, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven-University of Leuven, Herestraat 49, box 1044, 3000, Leuven, Belgium.
Laboratory of Immunoregulation, VIB Center for Inflammation Research, Department of Internal Medicine, Ghent University, Technologiepark 927, 9052, Ghent, Belgium.
Malar J. 2018 Mar 5;17(1):102. doi: 10.1186/s12936-018-2251-3.
Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a complication of malaria with a lethality rate of up to 80% despite anti-malarial treatment. It is characterized by a vast infiltration of leukocytes, microhaemorrhages and vasogenic oedema in the lungs. Previously, a mouse model for MA-ARDS was developed by infection of C57BL/6 mice with the Edinburgh line NK65-E of Plasmodium berghei.
Here, both host and parasite factors were demonstrated to play crucial roles in the development and severity of lung pathology. In particular, the genetic constitution of the host was an important determinant in the development of MA-ARDS. Both male and female C57BL/6, but not BALB/c, mice developed MA-ARDS when infected with P. berghei NK65-E. However, the New York line of P. berghei NK65 (NK65-NY) did not induce demonstrable MA-ARDS, despite its accumulation in the lungs and fat tissue to a similar or even higher extent as P. berghei NK65-E. These two commonly used lines of P. berghei differ in their red blood cell preference. P. berghei NK65-NY showed a stronger predilection for reticulocytes than P. berghei NK65-E and this appeared to be associated with a lower pathogenicity in the lungs. The pulmonary pathology in the C57BL/6/P. berghei NK65-E model was more pronounced than in the model with infection of DBA/2 mice with P. berghei strain ANKA. The transient lung pathology in DBA/2 mice infected with P. berghei ANKA coincided with the infection phase in which parasites mainly infected normocytes. This phase was followed by a less pathogenic phase in which P. berghei ANKA mainly infected reticulocytes.
The propensity of mice to develop MA-ARDS during P. berghei infection depends on both host and parasite factors and appears to correlate with RBC preference. These data provide insights in induction of MA-ARDS and may guide the choice of different mouse-parasite combinations to study lung pathology.
疟疾相关的急性呼吸窘迫综合征（MA-ARDS）是疟疾的一种并发症，即使接受抗疟治疗，其死亡率仍高达 80%。它的特征是肺部有大量白细胞浸润、微出血和血管源性水肿。此前，通过感染 C57BL/6 小鼠的爱丁堡 NK65-E 株伯氏疟原虫建立了 MA-ARDS 的小鼠模型。
在这里，宿主和寄生虫因素都被证明在肺部病理的发展和严重程度中起着关键作用。特别是，宿主的遗传构成是 MA-ARDS 发展的重要决定因素。感染伯氏疟原虫 NK65-E 的 C57BL/6 雄性和雌性小鼠均发展为 MA-ARDS，但 BALB/c 小鼠则不会。然而，伯氏疟原虫 NK65 的纽约株（NK65-NY）尽管在肺部和脂肪组织中的蓄积程度与伯氏疟原虫 NK65-E 相似，甚至更高，但并未导致明显的 MA-ARDS。这两种常用的伯氏疟原虫株在其红细胞偏好性方面存在差异。与伯氏疟原虫 NK65-E 相比，伯氏疟原虫 NK65-NY 对网织红细胞的亲和力更强，这似乎与肺部的低致病性有关。在 C57BL/6/P. berghei NK65-E 模型中，肺部病理比感染 DBA/2 小鼠的伯氏疟原虫 ANKA 模型更为明显。在感染伯氏疟原虫 ANKA 的 DBA/2 小鼠中短暂的肺部病理与寄生虫主要感染正常红细胞的感染阶段相吻合。随后是一个较少致病性的阶段，在此阶段，伯氏疟原虫 ANKA 主要感染网织红细胞。
在感染伯氏疟原虫时，小鼠发生 MA-ARDS 的倾向取决于宿主和寄生虫因素，并似乎与 RBC 偏好相关。这些数据提供了对 MA-ARDS 诱导的深入了解，并可能指导选择不同的小鼠-寄生虫组合来研究肺部病理。
