Figure 1. A brief summary of known (1-3) vs proposed (4-7) priming mechanisms from recent studies.

(1) Humoral response: (a) Activation of IMD- (immune deficiency), Toll- (TLR-like receptor), and JAK/STAT (Janus kinase signal transducer and activator of transcription) signalling pathways leading to synthesis & production of inducible AMPs (Sheehan et al., 2020) such as Attacins, Defensins & Coleoptericins in flour beetles (Greenwood et al., 2017; Ferro et al., 2019); Cecropins in fruit flies (Chakrabarti and Visweswariah, 2020); Cecropin, Attacin, Gloverin, Moricin & Lysozyme in silkworms (Yi et al., 2019); Gallerimycin & Galiomicin in wax-moths (Bergin et al., 2006); Cecropin in tobacco moths (Roesel et al., 2020) (b) Upregulated PGRP-SC (peptidoglycan recognition proteins - receptor for IMD pathway) and GNBPs (gram-negative binding proteins - receptor for Toll-pathway) in flour beetles (Ferro et al., 2019); Downregulated PGRP-LB (negative regulator of IMD-pathway) in fruit flies (Bozler et al., 2019) (c) Phenoloxidase (PO) response: Increased PO activity in flour beetles and mealworm beetles (Tetreau et al., 2019); Increased DDC (dopa-decarboxylase – a gene involved in PO cascade) in flour beetles (Ferro et al., 2019). (d) RNAi-pathway mediated specific priming against viral pathogens in fruit flies (Mondotte et al., 2018). (2) Cellular immunity: Increased phagocytosis activity (Pham et al., 2007; Weavers et al., 2016) and production of lamellocytes (Bozler et al., 2019) in fruit flies; Haemocyte differentiation induced by lipoxin (a lipid carrier) in mosquitoes (Rodrigues et al., 2010; Ramirez et al., 2015). (3) Down syndrome cell adhesion molecule (Dscam): Suspected role in specific immunity of flour beetles, fruit flies and other insects (Armitage et al., 2015); Acts as receptor during phagocytosis in crabs (Li et al., 2018); Upregulated in primed silkworms (Yi et al., 2019). (4) Epithelial response: Activation of haemocytes via intracellular accumulation of H₂O₂ (hydrogen peroxide) produced by DUOX (Reactive oxygen species producing dual-oxidase) through Toll & JAK/STAT pathway activation & Draper (damage associated signal molecules) in fruit flies (Chakrabarti and Visweswariah, 2020) (5) Metabolism and energetics: Downregulated metabolism-associated genes - hexokinase type 2 and sedoheptulokinase in flour beetles (Ferro et al., 2019); Upregulated trehalose transporter, GDP-D-glucose phosphorylase in mosquito Anopheles. albimanus (Maya-Maldonado et al., 2021) (6) Host-associated microbiota: Loss of priming in flour beetles (Futo et al., 2017) and Anopheles. gambiae mosquitoes (Rodrigues et al., 2010) after depleting microbiota. (7) Epigenetic mechanisms and reprogramming: Upregulated histone H3 gene, RNA polymerase II (transcription subunit 15) & exosome complex exonuclease (RRP6-like) (Ferro et al., 2019); Upregulated lncRNAs (long non-coding RNAs – necessary for regulating- metabolic, immune signalling and epigenetic processes (Ali et al., 2019) in flour beetles.