Immune challenge reduces gut microbial diversity and triggers fertility-dependent gene expression changes in a social insect

Abstract

Background The gut microbiome can influence life history traits associated with host fitness such as fecundity and longevity. In most organisms, these two life history traits are traded-off, while they are positively linked in social insects. In ants, highly fecund queens can live for decades, while their non-reproducing workers exhibit much shorter lifespans. Yet, when fertility is induced in workers by death or removal of the queen, worker lifespan can increase. It is unclear how this positive link between fecundity and longevity is achieved and what role the gut microbiome and the immune system play in this. To gain insights into the molecular regulation of lifespan in social insects, we investigated fat body gene expression and gut microbiome composition in workers of the ant Temnothorax rugatulus in response to an experimental induction of fertility and an immune challenge. Results Fertile workers upregulated several molecular repair mechanisms, which could explain their extended lifespan. The immune challenge altered the expression of several thousand genes in the fat body, including many immune genes, and, interestingly, this transcriptomic response depended on worker fertility. For example, only fertile, immune-challenged workers upregulated genes involved in the synthesis of alpha-ketoglutarate, an immune system regulator, which extends the lifespan in Caenorhabditis elegans by down-regulating the TOR pathway and reducing oxidant production. Additionally, we observed a dramatic loss in bacterial diversity in the guts of the ants within a day of the immune challenge. Yet, bacterial density did not change, so that the gut microbiomes of many immune challenged workers consisted of only a single or a few bacterial strains. Moreover, the expression of immune genes was linked to the gut microbiome composition, suggesting that the ant host can regulate the microbiome in its gut. Conclusions Immune system flare-ups can have negative consequence on gut microbiome diversity, pointing to a previously underrated cost of immunity. Moreover, our results provide important insights into shifts in the molecular regulation of fertility and longevity associated with insect sociality.

Histone acetylation regulates the expression of genes involved in worker reproduction and lifespan in the ant Temnothorax rugatulus

“…We removed queens from their colonies while feeding the workers with chemical inhibitors of histone acetylation (C646) or deacetylation (TSA). Our phenotypic and transcriptomic results confirmed that worker fecundity and survival increased after queen removal, as shown before in this species (Negroni et al, 2021(Negroni et al, , 2020. However, the ovary development of queenless workers was impaired when treated with the chemical inhibitors.…”

“…Ant workers start to reproduce and live longer after the loss of their queen in many ant species (Heinze, 2008;Kohlmeier et al, 2017;Konrad, Pamminger, & Foitzik, 2012) including our model Temnothorax rugatulus (Negroni et al, 2021(Negroni et al, , 2020. We took advantage of this plasticity by inducing fecundity in workers using queen removal and confirmed that workers in queenless colonies developed their ovaries, started laying eggs, survived better, and shifted their gene expression in the fat body.…”

“…We investigated where our "vitellogenin-1-like" copy falls within the vitellogeninphylogeny (Kohlmeier et al, 2018, data not shown) and found that it clusters close to the conventional vitellogenins , indicating an ancestral fecundity function as an egg yolk precursor (Amdam et al, 2003) rather than a derived role, as in worker caste differentiation (Feldmeyer, Elsner, & Foitzik, 2014;Morandin et al, 2014). Interestingly, a previous study on the effect of queen removal on worker gene expression in T. rugatulus detected a vitellogeninreceptor to be upregulated in fertile, queenless workers (Negroni et al, 2020), pointing to the importance of vg -associated pathways for worker reproduction.…”

“…Queen loss first induces fights among workers, who establish a new reproductive hierarchy, develop their ovaries, and start laying haploid eggs Heinze, 2008;Monnin & Peeters, 1999). Reproduction has strong effects on the physiology and immunity of workers, who can become more resistant to oxidative stress and often live longer (dos Santos Conceição Lopes, Campbell, & Contrera, 2020;Kohlmeier et al, 2017;Majoe, Libbrecht, Foitzik, & Nehring, 2021;Negroni, Segers, Vogelweith, & Foitzik, 2020). These positive effects of reproduction have been linked to the activation of signaling pathways such as insulin/insulin-like growth factor (IIS), the target of rapamycin (mTOR), and the alpha-ketoglutarate (alpha-KG) (Negroni, Macit, Stoldt, Feldmeyer, & Foitzik, 2021).…”

“…Queens can live over ten years and their gene expression in the brain and fat body changes with age (Negroni, Foitzik, & Feldmeyer, 2019). Following queen loss, T. rugatulus workers are known to develop their ovaries, start laying haploid eggs, live longer, and show transcriptomic changes in the fat body, a physiologically active tissue (Negroni et al, 2021(Negroni et al, , 2020. Here, we asked whether histone acetylation is required for workers to plastically respond to queen loss by altering their ovary development and associated gene expression.…”