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参与调控秀丽隐杆线虫感染念珠菌中固有免疫的 microRNAs。

microRNAs Involved in the Control of Innate Immunity in Candida Infected Caenorhabditis elegans.

机构信息

Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School, Southeast University, Nanjing 210009, China.

出版信息

Sci Rep. 2016 Oct 31;6:36036. doi: 10.1038/srep36036.

Abstract

The role of microRNAs (miRNAs) in regulating innate immune response to Candida albicans infection in Caenorhabditis elegans is still largely unclear. Using small RNA SOLiD deep sequencing technique, we profiled the miRNAs that were dysregulated by C. albicans infection. We identified 16 miRNAs that were up-regulated and 4 miRNAs that were down-regulated in nematodes infected with C. albicans. Bioinformatics analysis implied that these dysregulated miRNAs may be involved in the control of many important biological processes. Using available mutants, we observed that mir-251 and mir-252 loss-of-function mutants were resistant to C. albicans infection, whereas mir-360 mutants were hypersensitive to C. albicans infection. The expression pattern of antimicrobial genes suggested that mir-251, mir-252, and mir-360 played crucial roles in regulating the innate immune response to C. albicans infection. Fungal burden might be closely associated with altered lifespan and innate immune response in mir-251, mir-252, and mir-360 mutants. Moreover, mir-251 and mir-252 might function downstream of p38 mitogen activated protein kinase (MAPK) or IGF-1/insulin-like pathway to regulate the innate immune response to C. albicans infection. Our results provide an important molecular basis for further elucidating how miRNA-mRNA networks may control the innate immune response to C. albicans infection.

摘要

微小 RNA(miRNAs)在调控秀丽隐杆线虫对白念珠菌感染的固有免疫反应中的作用尚不清楚。本研究采用小 RNA SOLiD 深度测序技术,分析了白念珠菌感染诱导的 miRNA 表达谱。结果发现,16 个 miRNA 上调,4 个 miRNA 下调。生物信息学分析提示这些差异表达的 miRNA 可能参与了许多重要生物学过程的调控。利用现有的突变体,我们观察到 mir-251 和 mir-252 功能丧失突变体对白色念珠菌感染具有抗性,而 mir-360 突变体对白色念珠菌感染则高度敏感。抗菌基因的表达谱提示 mir-251、mir-252 和 mir-360 在调控对白念珠菌感染的固有免疫反应中发挥重要作用。真菌负荷与 mir-251、mir-252 和 mir-360 突变体的寿命和固有免疫反应的改变密切相关。此外,mir-251 和 mir-252 可能通过 p38 丝裂原活化蛋白激酶(MAPK)或 IGF-1/胰岛素样途径发挥作用,调控对白念珠菌感染的固有免疫反应。本研究为进一步阐明 miRNA-mRNA 网络如何调控对白念珠菌感染的固有免疫反应提供了重要的分子基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce76/5086856/d43ff3449743/srep36036-f1.jpg

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