Knowing your friends: invertebrate innate immunity fosters beneficial bacterial symbioses

Key Points Traditionally, it has been thought that the main function of the innate immune system is to combat pathogens. However, accumulating evidence supports the idea that the immune system also serves an important role in establishing and maintaining beneficial symbioses between the host and the microbiota. Four model invertebrate animal systems that form stable, long-term associations with bacterial symbionts — the cnidarian Hydra spp., the bobtail squid, the medicinal leech and the pea aphid — highlight how the innate immune system shapes these symbioses. On the basis of studies using these models, we propose mechanisms by which symbionts and non-symbionts can be distinguished by these hosts. Many of these interactions are mediated through symbiont-derived microorganism-associated molecular patterns (MAMPs) and host-derived pattern recognition receptors (PRRs), which lead to downstream host signalling events and the regulation of host immune effectors. In several of the model systems, the cellular immune response, in the form of phagocytic haemocytes, plays an important part in mediating interactions with symbionts. In some invertebrates, these cells can distinguish between symbiotic and non-symbiotic bacteria, and some symbionts might also have mechanisms for avoiding phagocytosis. Acellular, chemical effectors such as antimicrobial peptides and reactive oxygen species can also have important roles in determining the composition of the microbial community. We propose three mechanisms by which invertebrate hosts can distinguish between symbionts and non-symbionts: reciprocal signalling involving MAMPs and PRRs; sequestration of symbionts to specialized organs, tissues and cells; and avoidance of integrating a MAMP response with a damage signal, which otherwise leads to a heightened immune response by the host. Invertebrates lack conventional antibody-based immunity but have the capacity to distinguish between symbionts and pathogens. In this Review, Nyholm and Graf describe how the innate immune system of four model invertebrates functions in the establishment and maintenance of bacterial symbioses. The innate immune system is present in all animals and is a crucial first line of defence against pathogens. However, animals also harbour large numbers of beneficial microorganisms that can be housed in the digestive tract, in specialized organs or on tissue surfaces. Although invertebrates lack conventional antibody-based immunity, they are capable of e