Dinoflagellate symbionts escape vomocytosis by host cell immune suppression

Abstract

Alveolata comprises diverse taxa of single-celled eukaryotes, many renowned for their ability to live inside animal cells. Notable examples are apicomplexan parasites and dinoflagellate symbionts, the latter of which power coral reef ecosystems. Although functionally distinct, they evolved from a common, free-living ancestor and must evade their hosts’ immune response for persistence. Both the initial cellular events that gave rise to this intracellular lifestyle and the role of host immune modulation in coral-dinoflagellate endosymbiosis are poorly understood. Here, we use a comparative approach in the cnidarian endosymbiosis model Aiptasia, which re-establishes endosymbiosis with free-living dinoflagellates every generation. We find that uptake of microalgae is largely indiscriminate, but non-symbiotic microalgae are expelled by vomocytosis, while symbionts induce host-cell innate immune suppression and form a LAMP1-positive niche. We demonstrate that exogenous immune stimulation results in symbiont expulsion and conversely, inhibition of canonical toll-like receptor (TLR) signaling enhances infection of host animals. Our findings indicate that symbiosis establishment is dictated by local innate immune suppression, to circumvent expulsion and promote niche formation. This work provides insight into the evolution of the cellular immune response and key steps involved in mediating endosymbiotic interactions.

Symbiosis maintenance in the facultative coral, Oculina arbuscula, relies on nitrogen cycling, cell cycle modulation, and immunity

“…Whether the reduction in symbiont densities re-activates the coral immune system, or if activation of the coral immune system prompts greater symbiont expulsion through vomocytotic/apoptotic mechanisms is not yet entirely clear. Prior work 31 , stimulated Aiptasia larvae with LPS to prompt an immune response, which consequently increased the number of expelled symbionts, suggesting that immune system activation prompts symbiont expulsion. This relationship, however, depended on the timing of LPS exposure relative to symbiont infection; only concurrent LSP exposure and symbiont infection led to later symbiont expulsion 31 .…”

“…Alternative methods for controlling symbiont densities are exocytosis/vomocytosis or induced apoptosis of symbiont-bearing cells 31 , 34 . Interestingly, aposymbiotic branches showed enrichment of several biological process terms associated with and including “regulation of exocytosis;” and cellular components terms for “secretory vesicles” that were upregulated in aposymbiotic branches (Table S4 ; Figure S6 ).…”

“…Recent work on the uptake and release of different species of microalgae by Aiptasia larvae showed expulsion of unwanted microalgae occurs primarily through vomocytosis—a process that is likely controlled through host innate immune pathways 31 . Symbiodiniaceae may escape this vomocytosis through suppression of toll-like receptor and MyD88 pathways of the host’s immune system 31 .…”

“…Recent work on the uptake and release of different species of microalgae by Aiptasia larvae showed expulsion of unwanted microalgae occurs primarily through vomocytosis—a process that is likely controlled through host innate immune pathways 31 . Symbiodiniaceae may escape this vomocytosis through suppression of toll-like receptor and MyD88 pathways of the host’s immune system 31 . Other studies looking at the immune system regulator NF-KB (which interacts with MyD88) have found that symbiosis establishment can prompt widespread inhibition of expression of NF-KB in Aiptasia 38 , 90 – 92 as well as other taxa, including corals 93 , salamanders 62 , and sponges 77 .…”

Cnidarian Pattern Recognition Receptor Repertoires Reflect Both Phylogeny and Life History Traits

“…Our data support the link between cnidarian NLRs and apoptosis as many of the effector domains found in cnidarian NLRs including CARD (94), ZU5 (96), DD (95), Because NLRs are involved not only in pathogen recognition but also in self/altered-self/non-self-recognition, traits such as coloniality and ability to form nutritional algal symbiosis may be linked to expansions in NLRs (18,113). A recent study indicates that in E. daiphana, a symbiotic anemone, microalgae are taken into the cell largely indiscriminately and the decision to retain these microalgae as symbionts or expel them likely occurs intracellularly (114). As intracellular PRRs, NLRs are great candidates for modulating interactions between the algal symbionts and the immune system of their cnidarian hosts during the establishment of symbiosis, a hypothesis with some support from transcriptomic studies (115).…”