Ecdysone Titer Determined by 3DE-3β-Reductase Enhances the Immune Response in the Silkworm

Abstract

Although recent studies have demonstrated that 20-hydroxyecdysone (20E), one of the two most important hormones for development, could promote the insect innate immune response, how insects regulate 20E titer to affect the immunity after suffering pathogen attack remains unknown. In this study, to our knowledge, we first found that 20E titer was significantly elevated after bacterial infection in the domesticated silkworm, Bombyx mori. Furthermore, the elevated 20E enhanced the silkworm innate immune system against invading bacteria via ecdysone receptor. During immune response, the expression of the silkworm 3-dehydroecdysone-3β-reductase (3DE-3β-reductase) that converts 3DE released from prothoracic glands into ecdysone was induced. RNA interference experiments suggested that 3DE-3β-reductase is essential to upregulate the 20E titer after bacterial infection. The rescue experiments showed that injection with the recombinant 3DE-3β-reductase protein can significantly elevate the 20E concentration and modulate the expressions of the silkworm immune-related genes. Taken together, 20E titer determined by 3DE-3β-reductase enhances the silkworm defense against the bacterial infection. Thus, our findings reveal an important role of the 20E synthesis pathway from 3DE in enhancing the silkworm immune response and have profound implications for the understanding of interaction mechanisms between insect hormone and immunity.

TmCactin plays an important role in Gram-negative and -positive bacterial infection by regulating expression of 7 AMP genes in Tenebrio molitor

“…We suggest this possibility since several studies in Drosophila and other insects have shown that the developmental hormones ecdysone and juvenile hormone regulate the expression of a number of genes involved in innate immune responses2526272829. Interestingly, one of these studies showed that in the Drosophila Malpighian tubules of both larvae and adults, AMPs respond to ecdysone very quickly in the absence of infection28.…”

Transcriptomic analysis at the first instar larval stage of nonmolting Bombyx mori mutant (a42)

“…In most lepidopteran insects, ecdysone (α‐MH) is secreted directly from prothoracic glands and is also synthesized from 3‐dehydroecdysone (3DE) in other tissue (Kiriishi, Rountree, Sakurai, & Gilbert, 1990; Milner & Rees, 1985; W. Sun, Shen, Zhou, & Zhang, 2016). 3DE is reduced to α‐MH by 3DE‐3β‐reductase in hemolymph, and then 20‐hydroxylase catalyzes the formation of 20E from α‐MH (Chen, Turner, & Rees, 1999; W. Sun et al, 2016). 3DE‐3β‐reductase is an important enzyme that participates in the ecdysteroid synthesis pathway (Dauphin‐Villemant, Böcking, Blais, Toullec, & Lafont, 1997; W. Sun et al, 2016).…”

“…3DE is reduced to α‐MH by 3DE‐3β‐reductase in hemolymph, and then 20‐hydroxylase catalyzes the formation of 20E from α‐MH (Chen, Turner, & Rees, 1999; W. Sun et al, 2016). 3DE‐3β‐reductase is an important enzyme that participates in the ecdysteroid synthesis pathway (Dauphin‐Villemant, Böcking, Blais, Toullec, & Lafont, 1997; W. Sun et al, 2016). In silkworms, BmAKR2E4 belongs to aldo–keto reductase (AKR) superfamily and has 3DE reductase activity (Yamamoto & Wilson, 2013).…”

A mechanistic framework to explain the immunosuppressive effects of neurotoxic pesticides on bees

“…In vertebrates, complex immune functions are orchestrated by a well‐documented neuroendocrinological, innate immune‐regulatory axis involving a wide range of neurotransmitters and hormones (Sternberg, ). There is now evidence for a functionally similar axis in invertebrates utilizing at least two major insect hormones, juvenile hormone (Amdam et al., ; Flatt et al., ; Pamminger, Treanor, & Hughes, ; Rolff & Siva‐Jothy, ; Tian et al., ) and ecdysone (Rus et al., ; Sun, Shen, Zhou, & Zhang, ; Tan, Vlisidou, & Wood, ), as well as a range of neurotransmitters, including serotonin (Qi et al., ) and octopamine (Adamo, ; for a comprehensive summary see Adamo, and Sternberg, ). These findings indicate that key functions of the invertebrate innate immune system are under direct neuroendocrinological control (similar to vertebrates), not only enabling the systemic orchestration of immune responses during acute infections, but also likely facilitating immune homoeostasis and appropriate adjustments during internal (nutrient) and external (environmental) stress events (Adamo, , ; Buchon et al., ; Demas, Adamo, & French, ).…”