Regulation of cnidarian-dinoflagellate mutualisms: Evidence that activation of a host TGFβ innate immune pathway promotes tolerance of the symbiont

Dev Comp Immunol. 2012 Dec;38(4):525-37. doi: 10.1016/j.dci.2012.08.008. Epub 2012 Sep 23.


Animals must manage interactions with beneficial as well as detrimental microbes. Immunity therefore includes strategies for both resistance to and tolerance of microbial invaders. Transforming growth factor beta (TGFβ) cytokines have many functions in animals including a tolerance-promoting (tolerogenic) role in immunity in vertebrates. TGFβ pathways are present in basal metazoans such as cnidarians but their potential role in immunity has never been explored. This study takes a two-part approach to examining an immune function for TGFβ in cnidarians. First bioinformatic analyses of the model anemone Aiptasia pallida were used to identify TGFβ pathway components and explore the hypothesis that an immune function for TGFβs existed prior to the evolution of vertebrates. A TGFβ ligand from A. pallida was identified as one that groups closely with vertebrate TGFβs that have an immune function. Second, cellular analyses of A. pallida were used to examine a role for a TGFβ pathway in the regulation of cnidarian-dinoflagellate mutualisms. These interactions are stable under ambient conditions but collapse under elevated temperature, a phenomenon called cnidarian bleaching. Addition of exogenous human TGFβ suppressed an immune response measured as LPS-induced nitric oxide (NO) production by the host. Addition of anti-TGFβ to block a putative TGFβ pathway resulted in immune stimulation and a failure of the symbionts to successfully colonize the host. Finally, addition of exogenous TGFβ suppressed immune stimulation in heat-stressed animals and partially abolished a bleaching response. These findings suggest that the dinoflagellate symbionts somehow promote host tolerance through activation of tolerogenic host immune pathways, a strategy employed by some intracellular protozoan parasites during their invasion of vertebrates. Insight into the ancient, conserved nature of host-microbe interactions gained from this cnidarian-dinoflagellate model is valuable to understanding the evolution of immunity and its role in the regulation of both beneficial and detrimental associations.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bayes Theorem
  • Conserved Sequence
  • Dinoflagellida / physiology*
  • Heat-Shock Response
  • Immunity, Innate*
  • Likelihood Functions
  • Lipopolysaccharides / pharmacology
  • Models, Genetic
  • Molecular Sequence Data
  • Nitric Oxide / metabolism
  • Phylogeny
  • Sea Anemones / immunology*
  • Sea Anemones / metabolism
  • Signal Transduction
  • Smad Proteins / genetics
  • Smad Proteins / metabolism
  • Symbiosis / immunology*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / physiology


  • Lipopolysaccharides
  • Smad Proteins
  • Transforming Growth Factor beta
  • Nitric Oxide