# Dual interference with host neuropeptide signaling allows parasitoid wasp to hijack host sugar metabolism

## TL;DR

A parasitoid wasp manipulates its host's sugar metabolism using neuropeptides to increase trehalose levels, affecting the host's physiology.

## Contribution

The study reveals how parasitoid wasps use dual interference with host neuropeptide signaling to control sugar metabolism.

## Key findings

- Parasitoid wasp sNPF promotes glycogenolysis in the host fat body via the sNPFR.
- A symbiotic virus activates host sNPF expression, stimulating glycolysis in the midgut.
- Host and parasite sNPFs activate distinct downstream signaling pathways via different receptor affinities.

## Abstract

Changes in host carbohydrate metabolism determine the outcome of host–parasite relationships, but the underlying mechanistic basis remains elusive. Here, we show that the parasitoid wasp Cotesia vestalis induces trehalose accumulation in its host, the moth Plutella xylostella, largely independently of insulin/adipokinetic hormone signalling and food intake. Instead, parasitoids rewire host carbohydrate metabolism via two pathways activated by the evolutionarily conserved short neuropeptide F (sNPF), a functional analogue of mammalian neuropeptide Y. Parasitoid-derived teratocytes secrete sNPF that interacts with the sNPF receptor (sNPFR) on host cells, and contributes to host hypertrehalosemia by promoting glycogenolysis in the fat body. We further find that a parasitoid-symbiotic virus induces expression of host-encoded sNPF, which stimulates glycolysis in the host midgut. Furthermore, we show that the host sNPF-sNPFR complex stimulates Gq/Ca2+ signalling, while the parasitoid sNPF, exhibiting higher receptor affinity, triggers Gi/cAMP signalling. Molecular docking analyses suggest that the observed distinct receptor activation properties may be attributed to structural variations in the sNPF-sNPFR binding pocket. Collectively, our findings uncover an unexpected role of peripheral sNPFs in the regulation of carbohydrate metabolism during host–parasite interactions.

Carbohydrate metabolism influences the outcome of host-parasite relationships. This study shows that insect short neuropeptide F (sNPF) induces trehalose accumulation during the interaction between the parasitoid wasp Cotesia vestalis and its host, the moth Plutella xylostella.

sNPFs produced by both the host and the parasitoid act as trehalose-increasing hormones.Parasitoid-derived sNPF promotes glycogenolysis in the host fat body via the host sNPF receptor.Parasitoid-derived virus activates host sNPF expression, stimulating glycolysis in the midgut.Host and parasite sNPFs exhibit differing receptor affinities and stimulate distinct downstream signalling pathways.

sNPFs produced by both the host and the parasitoid act as trehalose-increasing hormones.

Parasitoid-derived sNPF promotes glycogenolysis in the host fat body via the host sNPF receptor.

Parasitoid-derived virus activates host sNPF expression, stimulating glycolysis in the midgut.

Host and parasite sNPFs exhibit differing receptor affinities and stimulate distinct downstream signalling pathways.

sNPFs derived from both the host and the parasite induce trehalose accumulation by targeting distinct host tissues and signalling pathways.