Induced Immune Reaction in the Acorn Worm, Saccoglossus kowalevskii, Informs the Evolution of Antiviral Immunity

Abstract

Evolutionary perspectives on the deployment of immune factors following infection have been shaped by studies on a limited number of biomedical model systems with a heavy emphasis on vertebrate species. Though their contributions to contemporary immunology cannot be understated, a broader phylogenetic perspective is needed to understand the evolution of immune systems across Metazoa. In our study, we leverage differential gene expression analyses to identify genes implicated in the antiviral immune response of the acorn worm hemichordate, Saccoglossus kowalevskii, and place them in the context of immunity evolution within deuterostomes – the animal clade composed of chordates, hemichordates, and echinoderms. Following acute exposure to the synthetic viral dsRNA analog, poly(I:C), we show that S. kowalevskii responds by regulating the transcription of genes associated with canonical innate immunity signaling pathways (e.g., NF-κB and IRF signaling) and metabolic processes (e.g., lipid metabolism), as well as many genes without clear evidence of orthology with those of model species. Aggregated across all experimental time point contrasts, we identify 423 genes that are differentially expressed in response to poly(I:C). We also identify 147 genes with altered temporal patterns of expression in response to immune challenge. By characterizing the molecular toolkit involved in hemichordate antiviral immunity, our findings provide vital evolutionary context for understanding the origins of immune systems within Deuterostomia.

Induction of apoptosis by double-stranded RNA was present in the last common ancestor of cnidarian and bilaterian animals

“…However, in some lineages it seems that the apoptotic response to dsRNA was lost. For instance, the hemichordate Saccoglossus kowalevskii did not exhibit a transcriptomic response to poly(I:C) [ 112 ]. Similarly, in the nematode C. elegans , which has been extensively studied in the context of apoptosis, dsRNA injection did not induce apoptosis [ 113 ].…”

“…vectensis , Homo sapiens , Mus musculus , S . kowalevskii , Crassostrea gigas , Branchiostoma belcheri , and Schmidtea mediterranea ) from diverse metazoan phylogenetic lineages [ 51 , 89 , 90 , 94 , 112 , 115 , 134 , 135 ]. Our analysis drew on results obtained from each corresponding study.…”

Induction of apoptosis by double-stranded RNA was present in the last common ancestor of cnidarian and bilaterian animals

“…To obtain a wider picture on the evolu�on of the an�viral apopto�c response in animals, we analyzed data from seven studies (Zhang, et al 2017;Hagai, et al 2018;Linehan, et al 2018;Lafont, et al 2020;Lewandowska, et al 2021;Bar Yaacov 2022;Tassia, et al 2023) focused on the gene expression response to immune challenges. These studies specifically employed poly (I:C) as a viral mimic.…”