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Overexpression of Toll-like receptor 4 contributes to the internalization and elimination of Escherichia coli in sheep by enhancing caveolae-dependent endocytosis

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Journal of Animal Science and Biotechnology 2021年第4期12卷 1323-1338页

作者： Yao Li Yue Zhao Xueling Xu Rui Zhang Jinlong Zhang Xiaosheng Zhang Yan Li Shoulong Deng Zhengxing Lian Beijing Key Laboratory for Animal Genetic Improvement National Engineering Laboratory for Animal BreedingKey Laboratory of Animal Genetics and Breeding of the Ministry of AgricultureCollege of Animal Science and TechnologyChina Agricultural UniversityBeijingChina Tianjin Institute of Animal Sciences TianjinChina State Key Laboratory of Agrobiotechnology College of Biological SciencesChina Agricultural UniversityBeijingChina Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina

Background:Gram-negative bacterial infections have a major economic impact on both the livestock industry and public ***-like receptor 4(TLR4)plays a crucial role in host defence against Gram-negative *** the defence mechanism regulated by TLR4 may provide new targets for treatment of inflammation and control of bacterial *** a previous study,we generated transgenic sheep overexpressing TLR4 by microinjection to improve disease *** defence mechanism through which TLR4 overexpression protected these sheep against pathogens is still not fully ***:In the present study,we used Escherichia coli to infect monocytes isolated from peripheral blood of the animal *** overexpression of TLR4 strongly enhanced the percentage of endocytosis and capacity of elimination in monocytes during the early stages of *** phenomenon was mainly due to overexpression of TLR4 promoting caveolae-mediated *** of the transgenic sheep monocytes with inhibitors of TLR4,Src signalling,or the caveolae-mediated endocytosis pathway reduced the internalization of bacteria,weakened the ability of the monocytes to eliminate the bacteria,and increased the pH of the ***:Together,our results reveal the effects of TLR4 on the control of *** infection in the innate immunity of sheep and provide crucial evidence of the caveolae-mediated endocytosis pathway required for host resistance to invading bacteria in a large animal model,providing theoretical support for breeding disease resistance in the ***,Src and caveolin 1(CAV1)could be potentially valuable targets for the control of infectious diseases.

关键词： caveolae-dependent endocytosis Host defence infection Inflammatory responses Monocytes Toll-like receptor 4

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