Parental experience with parasites and pathogens can lead to increased offspring resistance to infection, through a process known as transgenerational immune priming (TGIP). Broadly defined, TGIP occurs across a wide range of taxa, and can be viewed as a type of phenotypic plasticity, with hosts responding to the pressures of relevant local infection risk by altering their offspring's immune defenses. There are ever increasing examples of both invertebrate and vertebrate TGIP, which go beyond classical examples of maternal antibody transfer. Here we critically summarize the current evidence for TGIP in both invertebrates and vertebrates. Mechanisms underlying TGIP remain elusive in many systems, but while it is unlikely that they are conserved across the range of organisms with TGIP, recent insight into epigenetic modulation may challenge this view. We place TGIP into a framework of evolutionary ecology, discussing costs and relevant environmental variation. We highlight how the ecology of species or populations should affect if, where, when, and how TGIP is realized. We propose that the field can progress by incorporating evolutionary ecology focused designs to the study of the so far well chronicled, but mostly descriptive TGIP, and how rapidly developing -omic methods can be employed to further understand TGIP across taxa.

The transfer of immunity from parents to offspring (trans-generational immune priming (TGIP)) boosts offspring immune defence and parasite resistance. TGIP is usually a maternal trait. However, if fathers have a physical connection to their offspring, and if offspring are born in the paternal parasitic environment, evolution of paternal TGIP can become adaptive. In Syngnathus typhle, a sex-role reversed pipefish with male pregnancy, both parents invest into offspring immune defence. To connect TGIP with parental investment, we need to know how parents share the task of TGIP, whether TGIP is asymmetrically distributed between the parents, and how the maternal and paternal effects interact in case of biparental TGIP. We experimentally investigated the strength and differences but also the costs of maternal and paternal contribution, and their interactive biparental influence on offspring immune defence throughout offspring maturation. To disentangle maternal and paternal influences, two different bacteria were used in a fully reciprocal design for parental and offspring exposure. In offspring, we measured gene expression of 29 immune genes, 15 genes associated with epigenetic regulation, immune cell activity and life-history traits. We identified asymmetric maternal and paternal immune priming with a dominating, long-lasting paternal effect. We could not detect an additive adaptive biparental TGIP impact. However, biparental TGIP harbours additive costs as shown in delayed sexual maturity. Epigenetic regulation may play a role both in maternal and paternal TGIP.

In vertebrates, maternal transfer of immunity via the eggs or placenta provides offspring with crucial information on prevailing pathogens and parasites. Males contribute little to such transgenerational immune priming, either because they do not share the environment and parasite pressure of the offspring or because sperm are too small for transfer of immunity. In the teleost group of Syngnathids (pipefish, seahorses, and sea dragons), males brood female eggs in a placenta-like structure. Such sex-role-reversed species provide a unique opportunity to test for adaptive plasticity in immune transfer. Here, males and females should both influence offspring immunity. We experimentally tested paternal effects on offspring immunity by examining immune cell proliferation and immune gene expression. Maternal and paternal bacterial exposure induced offspring immune defense 5 weeks after hatching, and this effect persisted in 4-month-old offspring. For several offspring immune traits, double parental exposure (maternal and paternal) enhanced the response, whereas for another group of immune traits, the transgenerational induction already took place if only one parent was exposed. Our study shows that sex role reversal in connection with male pregnancy opens the door for biparental influences on offspring immunity and may represent an additional advantage for the evolution of male pregnancy.

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While originally acquired from the environment, a fraction of the microbiota is transferred from parents to offspring. The immune system shapes the microbial colonization, while commensal microbes may boost host immune defences. Parental transfer of microbes in viviparous animals remains ambiguous, as the two transfer routes (transovarial vs. pregnancy) are intermingled within the maternal body. Pipefishes and seahorses (syngnathids) are ideally suited to disentangle transovarial microbial transfer from a contribution during pregnancy due to their maternal egg production and their unique male pregnancy. We assessed the persistency and the changes in the microbial communities of the maternal and paternal reproductive tracts over proceeding male pregnancy by sequencing microbial 16S rRNA genes of swabs from maternal gonads and brood pouches of non-pregnant and pregnant fathers. Applying parental immunological activation with heat-killed bacteria, we evaluated the impact of parental immunological status on microbial development. Our data indicate that maternal gonads and paternal brood pouches harbor distinct microbial communities, which could affect embryonal development in a sex-specific manner. Upon activation of the immune system, a shift of the microbial community was observed. The activation of the immune system induced the expansion of microbiota richness during late pregnancy, which corresponds to the time point of larval mouth opening, when initial microbial colonization must take place.

BackgroundPhenotypic changes in response to environmental influences can persist from one generation into the next. In many systems parental parasite experience influences offspring immune responses, known as transgenerational immune priming (TGIP). TGIP in vertebrates is mainly maternal and short-term, supporting the adaptive immune system of the offspring during its maturation. However, if fathers and offspring have a close physical connection, evolution of additional paternal immune priming can be adaptive. Biparental TGIP may result in maximized immunological protection. Here, we investigate multigenerational biparental TGIP in the sex-role reversed pipefish Syngnathus typhle by exposing grandparents to an immune challenge with heat-killed bacteria and assessing gene expression (44 target genes) of the F2-generation.ResultsGrandparental immune challenge induced gene expression of immune genes in one-week-old grandoffspring. Similarly, genes mediating epigenetic regulation including DNA-methylation and histone modifications were involved in grandparental immune priming. While grand-maternal impact was strong on genes of the complement component system, grand-paternal exposure changed expression patterns of genes mediating innate immune defense.ConclusionIn a system with male pregnancy, grandparents influenced the immune system of their grandoffspring in a sex-specific manner, demonstrating multigenerational biparental TGIP. The involvement of epigenetic effects suggests that TGIP via the paternal line may not be limited to the pipefish system that displays male pregnancy. While the benefits and costs of grandparental TGIP depend on the temporal heterogeneity of environmental conditions, multigenerational TGIP may affect host-parasite coevolution by dampening the amplitude of Red Queen Dynamics.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-017-0885-3) contains supplementary material, which is available to authorized users.

Background Increases in ocean temperatures and in the frequency and severity of hypoxic events are expected with climate change, and may become a challenge for cultured Atlantic salmon and negatively affect their growth, immunology and welfare. Thus, we examined how an incremental temperature increase alone (Warm & Normoxic-WN: 12 → 20 °C; 1 °C week− 1), and in combination with moderate hypoxia (Warm & Hypoxic-WH: ~ 70% air saturation), impacted the salmon’s hepatic transcriptome expr\ession compared to control fish (CT: 12 °C, normoxic) using 44 K microarrays and qPCR. Results Overall, we identified 2894 differentially expressed probes (DEPs, FDR < 5%), that included 1111 shared DEPs, while 789 and 994 DEPs were specific to WN and WH fish, respectively. Pathway analysis indicated that the cellular mechanisms affected by the two experimental conditions were quite similar, with up-regulated genes functionally associated with the heat shock response, ER-stress, apoptosis and immune defence, while genes connected with general metabolic processes, proteolysis and oxidation-reduction were largely suppressed. The qPCR assessment of 41 microarray-identified genes validated that the heat shock response (hsp90aa1, serpinh1), apoptosis (casp8, jund, jak2) and immune responses (apod, c1ql2, epx) were up-regulated in WN and WH fish, while oxidative stress and hypoxia sensitive genes were down-regulated (cirbp, cyp1a1, egln2, gstt1, hif1α, prdx6, rraga, ucp2). However, the additional challenge of hypoxia resulted in more pronounced effects on heat shock and immune-related processes, including a stronger influence on the expression of 14 immune-related genes. Finally, robust correlations between the transcription of 19 genes and several phenotypic traits in WH fish suggest that changes in gene expression were related to impaired physiological and growth performance. Conclusion Increasing temperature to 20 °C alone, and in combination with hypoxia, resulted in the differential expression of genes involved in similar pathways in Atlantic salmon. However, the expression responses of heat shock and immune-relevant genes in fish exposed to 20 °C and hypoxia were more affected, and strongly related to phenotypic characteristics (e.g., growth). This study provides valuable information on how these two environmental challenges affect the expression of stress-, metabolic- and immune-related genes and pathways, and identifies potential biomarker genes for improving our understanding of fish health and welfare.

The marine environment is predicted to become warmer and more hypoxic, and these conditions may become a challenge for marine fish species. Phenotypically plastic responses facilitating acclimatization to changing environments can be mediated by DNA methylation through the modulation of gene expression. To investigate whether temperature and hypoxia exposure induce DNA methylation changes, we challenged post-smolt Atlantic salmon (Salmo salar) to increasing temperatures (12 → 20°C, 1°C week–1) under normoxia or moderate hypoxia (∼70% air saturation) and compared responses in the liver after 3 days or 4 weeks at 20°C. DNA methylation was studied in six genes related to temperature stress (cirbp, serpinh1), oxidative stress (prdx6, ucp2), apoptosis (jund), and metabolism (pdk3). Here, we report that exposure to high temperature, alone or combined with hypoxia, affected the methylation of CpG sites within different genomic regulatory elements around the transcription start of these temperature/hypoxia biomarker genes. Yet, we uncovered distinct CpG methylation profiles for each treatment group, indicating that each environmental condition may induce different epigenetic signatures. These CpG methylation responses were strongly dependent on the duration of stress exposure, and we found reversible, but also persistent, CpG methylation changes after 4 weeks of exposure to 20°C. Further, several of these changes in CpG methylation correlated with transcriptional changes, and thus, can be considered as regulatory epigenetic marks (epimarkers). Our study provides insights into the dynamic associations between CpG methylation and transcript expression in Atlantic salmon, and suggests that this epigenetic mechanism may mediate physiological acclimation to short-term and long-term environmental changes.