Metabolism and immune memory in invertebrates: are they dissociated?

Abstract

Since the discovery of specific immune memory in invertebrates, researchers have investigated its immune response to diverse microbial and environmental stimuli. Nevertheless, the extent of the immune system's interaction with metabolism, remains relatively enigmatic. In this mini review, we propose a comprehensive investigation into the intricate interplay between metabolism and specific immune memory. Our hypothesis is that cellular endocycles and epigenetic modifications play pivotal roles in shaping this relationship. Furthermore, we underscore the importance of the crosstalk between metabolism and specific immune memory for understanding the evolutionary costs. By evaluating these costs, we can gain deeper insights into the adaptive strategies employed by invertebrates in response to pathogenic challenges. Lastly, we outline future research directions aimed at unraveling the crosstalk between metabolism and specific immune memory. These avenues of inquiry promise to illuminate fundamental principles governing host-pathogen interactions and evolutionary trade-offs, thus advancing our understanding of invertebrate immunology.

Keywords: ecoimmunology; host-parasite relationship; immune priming; immunometabolism; innate immune response; specific memory; trade-offs.

Figure 1

lmmunometabolic relationship established within an immunocompetent invertebrate cell in response to the recognition of metabolic and immune stimuli. Initially, the recognition of insulin-like peptides (ILPs) by the insulin receptor (InR, Chico) activates the insulin signaling pathway (ISP). This activation triggers the PI3K signaling pathway (Phosphoinositide 3-kinase), which, in the case of mTOR activation (mammalian target of rapamycin), culminates in the activation of HIF1α/β (Hypoxia-Inducible Factor 1α/β) for the synthesis of the Dif dimer (Dorsal related immunity factor) and Dorsal (a member of the Rel transcription factor family) to form NF-κB involved in antimicrobial peptide (AMP) synthesis. In the case of AKT pathway activation (Serine-threonine kinase), which inhibits the activity of the FOXO transcription factor (forkhead box; O class transcription factor family), cellular growth, proliferation, differentiation, cellular longevity, and AMP synthesis are inhibited. Subsequently, following Toll receptor activation by the binding of the endogenous cytokine ligand Spätzle (an extracellular ligand of the Toll receptor) recognizing pathogen-associated molecular patterns (PAMPs) from Gram-negative bacteria (LPS-GNBP 1-3; β-1,3-glucan) and Gram-positive bacteria (Lipopolysaccharides bound to PGRP), the MyD88 adapter (myeloid differentiation factor 88) is activated, inducing the degradation of Inhibitor of κB (Cactus in Drosophila), favoring the translocation of the NF-κB nuclear factor and the synthesis of pattern recognition receptors (PRRs) and anti microbial peptide (AMP) genes, while also inhibiting PI3K activity. Finally, the activation of the immunocompetent cell through the Imd pathway (immune deficiency pathway), which activates Ird5 (IkB kinase homologue) and Relish (an NF-κB transcription factor, a key regulator of the Imd pathway) upon binding to PAMPs, LPS, and peptidoglycan through the PGRP-LC receptor (peptidoglycan recognition protein), culminates in NF-κB activation and the synthesis of target genes.