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

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 (TGF beta) cytokines have many functions in animals including a tolerance-promoting (tolerogenic) role in immunity in vertebrates. TGF beta 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 TGF beta in cnidarians. First bioinformatic analyses of the model anemone Aiptasia pallida were used to identify TGF beta pathway components and explore the hypothesis that an immune function for TGF beta s existed prior to the evolution of vertebrates. A TGF beta ligand from A. pallida was identified as one that groups closely with vertebrate TGF beta s that have an immune function. Second, cellular analyses of A. pallida were used to examine a role for a TGF beta 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 TGF beta suppressed an immune response measured as LPS-induced nitric oxide (NO) production by the host. Addition of anti-TGF beta to block a putative TGF beta pathway resulted in immune stimulation and a failure of the symbionts to successfully colonize the host. Finally, addition of exogenous TGF beta 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. (C) 2012 Elsevier Ltd. All rights reserved.