He Wei, Li Juan, Gong Ai-Yu, Deng Silu, Li Min, Wang Yang, Mathy Nicholas W, Feng Yaoyu, Xiao Lihua, Chen Xian-Ming
Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68198-5880, USA.
Microorganisms. 2021 Jan 12;9(1):151. doi: 10.3390/microorganisms9010151.
is a genus of that infect the gastrointestinal epithelium of a variety of vertebrate hosts. Intestinal epithelial cells are the first line of defense and play a critical role in orchestrating host immunity against infection. To counteract host defense response, has developed strategies of immune evasion to promote parasitic replication and survival within epithelial cells, but the underlying mechanisms are largely unclear. Using various models of intestinal cryptosporidiosis, we found that infection caused suppression of mitogen-activated protein kinase (MAPK) signaling in infected murine intestinal epithelial cells. Whereas expression levels of most genes encoding the key components of the MAPK signaling pathway were not changed in infected intestinal epithelial cells, we detected a significant downregulation of /, MAP kinase-activated protein kinase 2 (), and genes in infected host cells. Suppression of MAPK signaling was associated with an impaired intestinal epithelial defense against infection. Our data suggest that cryptosporidial infection may suppress intestinal epithelial cell MAPK signaling associated with the evasion of host antimicrobial defense.
是一类感染多种脊椎动物宿主胃肠道上皮的病原体。肠道上皮细胞是第一道防线，在协调宿主针对感染的免疫反应中起关键作用。为了对抗宿主防御反应，已发展出免疫逃避策略以促进在上皮细胞内的寄生复制和存活，但其潜在机制在很大程度上尚不清楚。利用各种肠道隐孢子虫病模型，我们发现感染导致受感染的小鼠肠道上皮细胞中丝裂原活化蛋白激酶（MAPK）信号传导受到抑制。虽然在受感染的肠道上皮细胞中，大多数编码MAPK信号通路关键成分的基因表达水平没有变化，但我们在受感染的宿主细胞中检测到/、丝裂原活化蛋白激酶激活的蛋白激酶2（）和基因的显著下调。MAPK信号传导的抑制与肠道上皮对感染的防御受损有关。我们的数据表明，隐孢子虫感染可能抑制与逃避宿主抗菌防御相关的肠道上皮细胞MAPK信号传导。
