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.