Insect cytokine paralytic peptide activates innate immunity via nitric oxide production in the silkworm Bombyx mori

Insect cytokine paralytic peptide (PP) upregulates the expression of immune-related genes and contributes to host defense in the silkworm Bombyx mori. The present findings demonstrated that PP promotes nitric oxide (NO) production and induces the expression of NO synthase. A pharmacologic NO synthase inhibitor suppressed the PP-dependent (i) induction of immune-related genes, (ii) activation of p38 mitogen-activated protein kinase, and (iii) killing delay of silkworm larvae by Staphylococcus aureus. The upstream mechanism of NO synthesis in insect immunity has been unknown, and the present results suggest for the first time that an insect cytokine induces NO and contributes to self-defense.

► An insect cytokine, PP, induced NOS expression in the silkworm fat body.
► Inhibition of NOS suppressed PP-dependent induction of immune-related genes.
► NO mediates PP-dependent p38 MAPK activation in the fat body.
► NOS function is necessary for the upregulation of host resistance induced by PP.