Center for Translational Research in Infection and Inflammation, Tulane School of Medicine, New Orleans, Louisiana, USA.
UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
JCI Insight. 2021 Jan 25;6(2):139573. doi: 10.1172/jci.insight.139573.
Pneumocystis is an important opportunistic fungus that causes pneumonia in children and immunocompromised individuals. Recent genomic data show that divergence of major surface glycoproteins may confer speciation and host range selectivity. On the other hand, immune clearance between mice and humans is well correlated. Thus, we hypothesized that humanize mice may provide information about human immune responses involved in controlling Pneumocystis infection. CD34-engrafted huNOG-EXL mice controlled fungal burdens to a greater extent than nonengrafted mice. Moreover, engrafted mice generated fungal-specific IgM. Fungal control was associated with a transcriptional signature that was enriched for genes associated with nonopsonic recognition of trophs (CD209) and asci (CLEC7A). These same genes were downregulated in CD4-deficient mice as well as twins with bare lymphocyte syndrome with Pneumocystis pneumonia.
卡氏肺孢子虫是一种重要的机会性真菌，可引起儿童和免疫功能低下者的肺炎。最近的基因组数据表明，主要表面糖蛋白的分化可能赋予种间和宿主范围选择性。另一方面，小鼠和人类之间的免疫清除作用相关性很好。因此，我们假设人源化小鼠可能提供有关控制卡氏肺孢子虫感染的人类免疫反应的信息。与未移植的小鼠相比，CD34 移植的 huNOG-EXL 小鼠更能控制真菌负荷。此外，移植的小鼠产生了真菌特异性 IgM。真菌的控制与一个转录特征相关，该特征富含与营养体（CD209）和子囊（CLEC7A）的非调理性识别相关的基因。在 CD4 缺陷小鼠以及患有卡氏肺孢子虫肺炎的裸淋巴细胞综合征双胞胎中，这些相同的基因也下调了。
