Abstract

A novel water-soluble polysaccharide was identified in the pupae of the melon fly (Bactrocera cucurbitae) as a molecule that activates the mammalian innate immune response. We attempted to purify this innate immune activator using nitric oxide (NO) production in mouse RAW264 macrophages as an indicator of immunostimulatory activity. A novel acidic polysaccharide was identified, which we named “dipterose”, with a molecular weight of 1.01×106 and comprising nine monosaccharides. Dipterose was synthesized in the melon fly itself at the pupal stage. The NO-producing activity of dipterose was approximately equal to that of lipopolysaccharide, a potent immunostimulator. Inhibition of Toll-like receptor 4 (TLR4) led to the suppression of NO production by dipterose. Furthermore, dipterose induced the expression of proinflammatory cytokines and interferon β (IFNβ) and promoted the activation of nuclear factor kappa B (NF-κB) in macrophages, indicating that it stimulates the induction of various cytokines in RAW264 cells via the TLR4 signaling pathway. Our results thus suggest that dipterose activates the innate immune response against various pathogenic microorganisms and viral infections. This is the first identification of an innate immune-activating polysaccharide from an animal.

Highlights

  • Insects have great potential as a source of food and feed [1] and a nutrition source that is comparable to meat and fish [2]

  • The recognition of pathogen components by macrophages leads to the production of cytokines and nitric oxide (NO), a cytotoxic molecule, which are essential for effective pathogen elimination [14, 26, 27]

  • We describe our identification of a water-soluble immune activator contained in extracts of melon fly pupae

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Summary

Introduction

Insects have great potential as a source of food and feed [1] and a nutrition source that is comparable to meat and fish [2]. It is noteworthy in this regard that various bioactive substances are found in numerous insect species with beneficial characteristics [4,5,6,7]. These substances include compounds with diverse pharmacological properties, including anticancer, anti-tumor, anti-viral, and anti-microbial activities and the capacity to enhance resistance to various diseases in humans, livestock, poultry, and fish [8,9,10,11,12]

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