Molecular Control of Innate Immune Response to Pseudomonas aeruginosa Infection by Intestinal let-7 in Caenorhabditis elegans

• Published in: PLoS pathogens 2017-01, Vol.13 (1), p.e1006152-e1006152
• Main Authors: Zhi, Lingtong, Yu, Yonglin, Li, Xueying, Wang, Daoyong, Wang, Dayong
• Format: Article
• Language: English
• Subjects: Animals; Biology and Life Sciences; Blotting, Western; Caenorhabditis elegans; Caenorhabditis elegans - immunology; Caenorhabditis elegans - microbiology; Care and treatment; Disease Models, Animal; Education; Funding; Gene expression; Gene Expression Regulation - immunology; Health aspects; Immune response; Immunity, Innate - immunology; Infections; Kinases; Laboratories; Medical schools; Medicine and Health Sciences; MicroRNA; MicroRNAs; MicroRNAs - immunology; Mutation; Nematoda; Nematodes; Proteins; Pseudomonas aeruginosa; Pseudomonas aeruginosa - immunology; Pseudomonas aeruginosa infections; Pseudomonas Infections - immunology; Real-Time Polymerase Chain Reaction; Signal transduction; Statistical analysis; Variance analysis
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1006152

The microRNA (miRNA) let-7 is an important miRNA identified in Caenorhabditis elegans and has been shown to be involved in the control of innate immunity. The underlying molecular mechanisms for let-7 regulation of innate immunity remain largely unclear. In this study, we investigated the molecular basis for intestinal let-7 in the regulation of innate immunity. Infection with Pseudomonas aeruginosa PA14 decreased let-7::GFP expression. Intestine- or neuron-specific activity of let-7 was required for its function in the regulation of innate immunity. During the control of innate immune response to P. aeruginosa PA14 infection, SDZ-24 was identified as a direct target for intestinal let-7. SDZ-24 was found to be predominantly expressed in the intestine, and P. aeruginosa PA14 infection increased SDZ-24::GFP expression. Intestinal let-7 regulated innate immune response to P. aeruginosa PA14 infection by suppressing both the expression and the function of SDZ-24. Knockout or RNA interference knockdown of sdz-24 dampened the resistance of let-7 mutant to P. aeruginosa PA14 infection. Intestinal overexpression of sdz-24 lacking 3'-UTR inhibited the susceptibility of nematodes overexpressing intestinal let-7 to P. aeruginosa PA14 infection. In contrast, we could observed the effects of intestinal let-7 on innate immunity in P. aeruginosa PA14 infected transgenic strain overexpressing sdz-24 containing 3'-UTR. In the intestine, certain SDZ-24-mediated signaling cascades were formed for nematodes against the P. aeruginosa PA14 infection. Our results highlight the crucial role of intestinal miRNAs in the regulation of the innate immune response to pathogenic infection.