Apoptosis in molluscan immune defense

Apoptosis, or Type I programmed cell death, is a fundamental biological process involved in cellular homeostasis in metazoans. Apoptosis plays a key role in immune system homeostasis and function, defense against parasite and pathogens and self/non-self recognition. In this review, I present our current knowledge of the mechanisms and signaling pathways underlying apoptosis in mollusks and its roles in host-pathogen interactions and immune defense. Both signaling and execution pathways of apoptosis appear to be highly conserved in mollusks, although there is evidence that some apoptotic mechanisms (e.g., caspase-independent cell death) may differ from model invertebrates such as Caenorhabditis and Drosophila and more closely resemble those seen in vertebrates. Apoptosis is important for the functioning of the molluscan immune system as indicated by the high baseline apoptosis rates observed in circulating and resident hemocytes. Apoptosis also plays a role in host protection against parasites by limiting the spread of the pathogen while preventing inflammatory damage of surrounding tissues. In molluscs, interaction between immune cells and parasites or pathogens usually triggers apoptosis; however, some pathogens (especially obligatory intracellular parasites that depend on the host cell for their survival and proliferation) can inhibit this response and prevent host cell death. Currently, the mechanisms underlying pathogen-induced modulation of apoptosis in molluscs are not well understood. Summarizing our current knowledge of the immune functions of apoptosis in molluscs, and comparing them with the more widely studied vertebrate systems, this review will delineate the gaps in our understanding of this critical cellular process in molluscs and assist in the ongoing search for evolutionary novel mechanisms of apoptosis in immune defense and self/non-self-recognition.