Immune priming: the secret weapon of the insect world

Abstract

Insects are a highly successful group of animals that inhabit almost every habitat and environment on Earth. Part of their success is due to a rapid and highly effective immune response that identifies, inactivates, and eliminates pathogens. Insects possess an immune system that shows many similarities to the innate immune system of vertebrates, but they do not possess an equivalent system to the antibody-mediated adaptive immune response of vertebrates. However, some insect do display a process known as immune priming in which prior exposure to a sublethal dose of a pathogen, or pathogen-derived material, leads to an elevation in the immune response rendering the insect resistant to a subsequent lethal infection a short time later. This process is mediated by an increase in the density of circulating hemocytes and increased production of antimicrobial peptides. Immune priming is an important survival strategy for certain insects while other insects that do not show this response may have colony-level behaviors that may serve to limit the success of pathogens. Insects are now widely used as in vivo models for studying microbial pathogens of humans and for assessing the in vivo efficacy of antimicrobial agents. Knowledge of the process of immune priming in insects is essential in these applications as it may operate and augment the perceived in vivo antimicrobial activity of novel compounds.Abbreviations: 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate; SBC3: antimicrobial peptides; AMPs: dorsal-related immunity factor; DIF: Down syndrome cell adhesion molecule; Dscam: Lipopolysaccharide; LPS: Pathogen-associated molecular patterns; PAMPS: Patterns recognition receptors; PRR: Prophenoloxidase; PO: Toll-like receptors; TLRs: Toll/IL-1R; TIR, Transgenerational Immune Priming; TgIP: Tumor necrosis factor-α; TNF-α.

Keywords: Galleria larvae; immunity; in vivo model; infection; priming.

Figure 1.

Comparision between mammalian and invertebrate Toll/Toll-like receptor and IMD/TNF-α signaling. Upon activation of invertebrate Toll receptor and the homologous Toll-like receptor in vertebrates, a cascade is induced where the homologous transcription factors Nf-κB and Dif are activated in vertebrates and invertebrates, respectively. The IMD pathway is activated by binding of peptidoglycan (PGN) to peptidoglycan-recognition proteins (PGRPs) which results in recruitment and formation of an IMD, dFADD and DREDD complex and results in IMD cleavage and activation of TAB2/TAK1. This results in Relish phosphorylation and ultimately the production of AMPs (e.g. cecropin). In mammals, TNF-α is bound by the tumor necrosis factor receptor 1 (TNF-R1) which results in recruitment of RIPP, FADD, and caspase 8. NF-κB is released from its inhibitor protein (IκB) via phosphorylation by IKK complex which results in NF-κB translocation to the nucleus resulting in pro-inflammatory cytokine production.

Figure 2.

Summary of immune priming in G. mellonella larvae. The effect of cells or cell component, antimicrobial agents or thermal and physical stress on immune priming in G. mellonella larvae. Components of the fungal cell wall (laminarin/β-glucan) or a sub-lethal C. albicans or S. cerevisiae infection protect from a subsequent potentially lethal infection by an increased abundance of AMPs and the number of circulating hemocytes. The antifungal agent caspofungin induced increased resistance to S. aureus infection. Gentle shaking and a 1 h 37°C incubation induces immune priming in larvae.