Many cnidarians, including the reef-building corals, undergo symbiotic mutualisms with photosynthetic dinoflagellate algae of the family Symbiodiniaceae. These partnerships are sensitive to temperature extremes, which cause symbiont loss and increased coral mortality.Previous studies have implicated host immunity and specifically immunity transcription factor NF-κB as having a role in the maintenance of the cnidarian-algal symbiosis. Here we have further investigated a possible role for NF-κB in establishment and loss of symbiosis in various strains of the anemone Exaiptasia (Aiptasia) and in the coral Pocillopora damicornis. Our results show that NF-κB expression is reduced in Aiptasia larvae and adults that host certain algae strains. Treatment of Aiptasia larvae with a known symbiosis-promoting cytokine, transforming growth factor β , also led to decreased NF-κB expression. We also show that aposymbiotic Aiptasia (with high NF-κB expression) have increased survival following infection with the pathogenic bacterium Serratia marcescens as compared to symbiotic Aiptasia (low NF-κB expression). Furthermore, a P. damicornis coral colony hosting Durusdinium spp. (formerly clade D) symbionts had higher basal NF-κB expression and decreased heat-induced bleaching as compared to two individuals hosting Cladocopium spp. (formerly clade C) symbionts. Lastly, genome-wide gene expression profiling and genomic promoter analysis identified putative NFκ B target genes that may be involved in thermal bleaching, symbiont maintenance, and/or immune protection in P. damicornis. Our results provide further support for the hypothesis that modulation of NF-κB and immunity plays a role in some, but perhaps not all, cnidarian-Symbiodiniaceae partnerships as well as in resistance to pathogens and bleaching. 2017; Mansfield et al., 2017; Williams et al., 2018). We and others have shown that the expression and activity of NF-κB are modulated during the onset of symbiosis and after loss of symbiosis in both Aiptasia (Wolfowicz et al., 2016; Mansfield et al., 2017) and the coral Acropora palmata (DeSalvo et al., 2010). For example, Mansfield et al. (2017) demonstrated that the establishment of algal symbiosis in naïve Aiptasia larvae is associated with a reduction in NF-κB expression and that heat-induced loss of symbiosis in adult Aiptasia is associated with increased NF-κB expression and DNA-binding activity. Furthermore, genomic analyses have shown that symbiotic cnidarians, such as the coral Pocillopora damicornis (Cunning et al., 2018), have extensive repertoires of immune signaling genes. Based on these data, we hypothesized that algal symbionts can modulate host NF-κB expression to effect a decrease in host immunity to allow for the establishment of symbiosis (Mansfield et al., 2017; Mansfield and Gilmore, 2019).Herein, we have used Aiptasia and P. damicornis to further investigate Symbiodiniaceaeinduced downregulation of NF-κB, as well as the implications of decreased NF-κB levels and symbiont type for cnidarian immunity and suscept...