biology Review Cnidarian Immunity and the Repertoire of Defense Mechanisms in Anthozoans Maria Giovanna Parisi 1,* , Daniela Parrinello 1, Loredana Stabili 2 and Matteo Cammarata 1,* 1 Department of Earth and Marine Sciences, University of Palermo, 90128 Palermo, Italy; [email protected] 2 Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy; [email protected] * Correspondence: [email protected] (M.G.P.); [email protected] (M.C.) Received: 10 August 2020; Accepted: 4 September 2020; Published: 11 September 2020 Abstract: Anthozoa is the most specious class of the phylum Cnidaria that is phylogenetically basal within the Metazoa. It is an interesting group for studying the evolution of mutualisms and immunity, for despite their morphological simplicity, Anthozoans are unexpectedly immunologically complex, with large genomes and gene families similar to those of the Bilateria. Evidence indicates that the Anthozoan innate immune system is not only involved in the disruption of harmful microorganisms, but is also crucial in structuring tissue-associated microbial communities that are essential components of the cnidarian holobiont and useful to the animal’s health for several functions including metabolism, immune defense, development, and behavior. Here, we report on the current state of the art of Anthozoan immunity. Like other invertebrates, Anthozoans possess immune mechanisms based on self/non-self-recognition. Although lacking adaptive immunity, they use a diverse repertoire of immune receptor signaling pathways (PRRs) to recognize a broad array of conserved microorganism-associated molecular patterns (MAMP). The intracellular signaling cascades lead to gene transcription up to endpoints of release of molecules that kill the pathogens, defend the self by maintaining homeostasis, and modulate the wound repair process. The cells play a fundamental role in immunity, as they display phagocytic activities and secrete mucus, which acts as a physicochemical barrier preventing or slowing down the proliferation of potential invaders. Finally, we describe the current state of knowledge of some immune effectors in Anthozoan species, including the potential role of toxins and the inflammatory response in the Mediterranean Anthozoan Anemonia viridis following injection of various foreign particles differing in type and dimensions, including pathogenetic bacteria. Keywords: cnidarians; innate immunity; Anthozoan; bioactive molecules; inflammatory response 1. Introduction Cnidarians are phylogenetically basal aquatic animals within the Metazoa, with radial symmetry and the first level of tissue organization. They are evolutionarily early-diverged Metazoa, some of whom can live for hundreds of years, which suggests that they are potentially exposed to some pathogens on many occasions during their lifespans [1]. It is difficult to explain how these long-lived organisms have done so well with only an innate immune system as the protective mechanism against infectious agents. Cnidarians are of great interest since they apply many of the same cellular pathways involved in innate immunity in mammals. They have a surprising amount of immune complexity, as they contain innate immune components that are lacking in other basal invertebrate groups [2]. Biology 2020, 9, 283; doi:10.3390/biology9090283 www.mdpi.com/journal/biology Biology 2020, 9, 283 2 of 26 Biology 2020, 9, x 2 of 25 In addition to pathogen recognition, the cnidarian innate immune system has a role in managing beneficialbeneficial microbes and and supporting supporting mutualistic mutualistic microbial microbial symbioses. symbioses. It Itregulates regulates the the maintenance maintenance of symbiosisof symbiosis and and takes takes on on the the task task of of discerning discerning be betweentween pathogens pathogens that that need need to to be be cleared versus beneficialbeneficial symbiotic symbiotic microbes microbes [3]. [3 ]. Anthozoa is the mostmost speciosespeciose classclass ofof Cnidaria,Cnidaria, includingincluding thethe subclassessubclasses HexacoralliaHexacorallia and Octocorallia, which which comprise comprise hard hard corals corals or or anemon anemoneses and and soft soft corals corals and and gorgonians gorgonians (Figure (Figure 1). 1). Figure 1. Cnidarian evolutionary history based on rRNA phylogenies. It isis wellwell knownknown thatthat AnthozoanAnthozoan epitheliaepithelia areare colonizedcolonized by aa communitycommunity ofof associatedassociated microorganisms that that influence influence animal animal development development and and host host fitness. fitness. Epithelium Epithelium colonization colonization is also is determinedalso determined by the by availability the availability of nutrients, of nutrients, and compet anditive competitive interactions interactions for the colonization for the colonization of the animal of substratethe animal by substrate different bysymbiotic different bacterial symbiotic strains. bacterial strains. Several immune immune response response genes genes have have been been cons conservederved from from cnidarians cnidarians to vertebrates to vertebrates [4–8]. [4– 8]. The immune system system of of cnidarians cnidarians is isbased based on on self self/non-self-recognition/non-self-recognition and andit is itcomprised is comprised of four of majorfour major functions: functions: the immune the immune recognition recognition regulated regulated by membrane by membrane pattern pattern recognition recognition receptors receptors (PRRs) (PRRs)that bind that to bindmolecular to molecular patterns patterns in pathogens in pathogens (MAMPs); (MAMPs); activation activation of a range of a of range transcription of transcription factor; intracellularfactor; intracellular signaling signaling cascades cascades leading to leading gene transc to geneription transcription and ultimately and ultimately protein translation; protein translation; endpoints ofendpoints release of of the release proteins of the and proteins molecu andles that molecules eliminate that the eliminate threat and the mitigate threat andself-harm, mitigate kill self-harm, the pathogen kill (antibacterialthe pathogen (antibacterialmolecules, reactive molecules, oxygen reactive molecules, oxygen molecules,antioxidant, antioxidant, phagocytosis, phagocytosis, and other and cellular other activities),cellular activities), and defend and self defend by maintaining self by maintaining homeostasis. homeostasis. These eeffectorsffectors areare antibacterialantibacterial molecules,molecules, reactive oxygenoxygen molecules,molecules, antioxidant,antioxidant, and cellularcellular activities. Finally, Finally, the the specimens specimens must must also also close close any any wounds wounds and and regenerate regenerate the thedestroyed destroyed tissues. tissues. The epithelial cellscells playplay aa fundamentalfundamental rolerole inin immunityimmunity as they display phagocytic activities and secrete mucus, which acts as a physicochemicalphysicochemical barrierbarrier preventing or slowing down the proliferation of potential pathogens pathogens [9,10]. [9,10]. The mucus contains several protecto protectorr factors, including serine protease inhibitors with bactericidal activity and antimicrobial antimicrobial peptides peptides (AMPs) (AMPs) [11,12]. [11,12]. The Anthozoans Anthozoans can can distinguish distinguish self self from from non-self non-self like like tissues tissues contiguous contiguous conspecifics conspecifics [13]. This [13]. Thisallorecognition allorecognition and xenorecognition and xenorecognition capability capability with related with killing related mechanisms killing mechanisms has been established has been in Hydrozoansestablished inand Hydrozoans Anthozoans and [14–16]. Anthozoans In the colonial [14–16]. cnidarians, In the colonial the allorecognition cnidarians, the process allorecognition limits the processfusion with limits genetically the fusion different with genetically individuals different as well individuals as the parasitic as well germ as the line, parasitic starting germ with line, a startingcontact withavoidance a contact response avoidance and culminatin response andg in culminatingthe usage of nematocysts. in the usage of nematocysts. As invertebrates who rely on the innate component of immunity, they should not be able to develop resistance toward a particular pathogen [17]. However, a form of immunological memory has long been Biology 2020, 9, 283 3 of 26 As invertebrates who rely on the innate component of immunity, they should not be able to develop resistance toward a particular pathogen [17]. However, a form of immunological memory has long been suggested in cnidarians, based on tissue allo- and xeno- transplants [18]. It is true that the mechanisms underlying recognition may differ from those involved in the functioning of the defense system. Further evidence of immunological memory derives from classes of receptors that recognize molecular models of different pathogens [19]. This means that Anthozoans can recognize the difference between pathogenic types, responding with specific binding receptors to acquire memory for a specific pathogen. Here, we reported the current state of knowledge about cellular and molecular immune repertoire in Anthozoan species and the inflammatory responses in Anemonia viridis (Cnidaria: Anthozoa) following bacterial injection and pathogenetic invasions with bacteria such as Escherichia coli and Vibrio alginolyticus.