A house fly TNF ortholog Eiger regulates immune defense via cooperating with Toll and Imd pathways

In mammals, the TNF family is important inflammatory cytokines. Eiger, the invertebrate ortholog of TNF identified firstly in Drosophila, has been implicated in immune response with an unknown molecular mechanism. The present work reports a novel eiger like gene (Mdeiger) from Musca domestica. Mdeiger was significantly up-regulated upon challenge with either Escherichia coli or Staphylococcus aureus. Silencing Mdeiger led to higher mortalities of larvae post either E. coli or S. aureus infection, enhanced the expressions of attacin and diptericin, but blocked the induction of ceropin and muscin, and inhibited the activation of phenoloxidase following bacterial challenge. Meanwhile, the expression of dorsal and JNK was inhibited while that of relish was enhanced in Mdeiger-depleted larvae. We suppose that, by coordinating with the Imd, Toll and JNK pathways, Mdeiger be involved in regulating the innate immune response through controlling the capacity of phenoloxidase and the expression of antimicrobial peptide genes synergistically.