Epigenetic Mechanisms Are Involved in Sex-Specific Trans-Generational Immune Priming in the Lepidopteran Model Host Manduca sexta

Abstract

Parents invest in their offspring by transmitting acquired resistance against pathogens that only the parents have encountered, a phenomenon known as trans-generational immune priming (TGIP). Examples of TGIP are widespread in the animal kingdom. Female vertebrates achieve TGIP by passing antibodies to their offspring, but the mechanisms of sex-specific TGIP in invertebrates are unclear despite increasing evidence suggesting that both male-specific and female-specific TGIP occurs in insects. We used the tobacco hornworm (Manduca sexta) to investigate sex-specific TGIP in insects because it is a model host for the analysis of insect immunity and the complete genome sequence is available. We found that feeding larvae with non-pathogenic Escherichia coli or the entomopathogen Serratia entomophila triggered immune responses in the infected host associated with shifts in both DNA methylation and histone acetylation. Maternal TGIP was mediated by the translocation of bacterial structures from the gut lumen to the eggs, resulting in the microbe-specific transcriptional reprogramming of genes encoding immunity-related effector molecules and enzymes involved in the regulation of histone acetylation as well as DNA methylation in larvae of the F1 generation. The third-instar F1 larvae displayed sex-specific differences in the expression profiles of immunity-related genes and DNA methylation. We observed crosstalk between histone acetylation and DNA methylation, which mediated sex-specific immune responses in the F1 generation derived from parents exposed to a bacterial challenge. Multiple routes for TGIP seem to exist in M. sexta and – partially sex-specific – effects in the offspring depend on the microbial exposure history of their parents. Crucially, the entomopathogen S. entomophila appears to be capable of interfering with TGIP in the host.

Silencing of the DNA methyltransferase 1 associated protein 1 (DMAP1) gene in the invasive ladybird Harmonia axyridis implies a role of the DNA methyltransferase 1‐DMAP1 complex in female fecundity

“…The F1eggs of the first filial generation (F1) laid by the F0 generation were kept at three different temperatures (15, 21 or 28 C) and the emerging beetles were tested to determine the frequency of each group. We then used RNA interference (RNAi) to silence genes encoding enzymes responsible for DNA methylation and histone acetylation/deacetylation, two epigenetic mechanisms that are known to regulate the initiation of transcription (Glastad et al, 2011;Vilcinskas, 2017;Gegner et al, 2019).…”

Trends in symbiont-induced host cellular differentiation

“…While we are still in the early days of characterizing how bacterial symbionts can epigenetically modify host cellular differentiation through chromatin modifications, a number of preliminary data points suggest that this will be a productive area of research in future years. For example, host-pathogen associations have been reported to have long-lasting or transgenerational effects, likely mediated through epigenetic mechanisms, although they have not yet been identified (Fridmann-Sirkis et al 2014;Mukherjee et al 2017;Yang et al 2018;Gegner et al 2019). Epigenetic-based gene regulation is also implicated in eukaryote-eukaryote mutualisms such as coral-algal symbioses (Li et al 2018).…”

Relish as a Candidate Marker for Transgenerational Immune Priming in a Dampwood Termite (Blattodae: Archeotermopsidae)

“…TGIP is most likely to evolve when the pathogen is predictable in time and space (i.e., likely to persist into the next generation [5,14]) and when hosts exhibit either limited dispersal and/or overlapping generations [4,15]. If so, we expect TGIP to manifest via parental transfer of prefabricated immune proteins [16], immune-related transcripts [17], immune-elicitors [18,19], altered epigenetic markers [20,21], or combinations thereof, ultimately rendering progeny less susceptible to disease [4,5]. For example, immune-primed mothers of Manduca sexta (Lepidoptera) can translocate pathogen-associated molecular patterns (PAMPs; molecular signatures unique to invading microbes) to their eggs [18,21] which, upon hatching, produce larvae with enhanced immune-related phenoloxidase expression and improved bacterial clearing capabilities [22,23].…”

“…If so, we expect TGIP to manifest via parental transfer of prefabricated immune proteins [16], immune-related transcripts [17], immune-elicitors [18,19], altered epigenetic markers [20,21], or combinations thereof, ultimately rendering progeny less susceptible to disease [4,5]. For example, immune-primed mothers of Manduca sexta (Lepidoptera) can translocate pathogen-associated molecular patterns (PAMPs; molecular signatures unique to invading microbes) to their eggs [18,21] which, upon hatching, produce larvae with enhanced immune-related phenoloxidase expression and improved bacterial clearing capabilities [22,23]. Similarly, offspring of Tenebrio castaneum (Coleoptera) show up-regulated antimicrobial peptides following maternal exposure to bacteria [24].…”