Cellular receptors and signal transduction in molluscan hemocytes: connections with the innate immune system of vertebrates

The involvement of circulating hemocytes as the principal cellulareffector mediating molluscan immune responses is well established.They participate in a variety of internal defense-related activitiesincluding microbial phagocytosis, multicellular encapsulation,and cell-mediated cytotoxicity reactions that are presumed tobe initiated through foreign ligand binding to hemocyte receptorsand subsequent transduction of the binding signal through thecell resulting in appropriate (or in some cases, inappropriate)hemocyte responses. At present, however, although functionalevidence abounds as to the existence of hemocyte "recognition"receptors, few have been characterized at the molecular level.Similarly, signal transduction systems associated with variousreceptor-mediated hemocyte functions in molluscs are only beginningto be investigated and understood. This review examines whatis currently known about the molluscan hemocyte receptors andthe putative signal transduction pathways involved in regulatingtheir cellular behaviors/activities. The cumulative data impliesthe presence of various hemocyte-associated receptors capableof binding specific carbohydrates, extracellular matrix proteins,growth factors, hormones, and cytokines. Moreover, receptor-ligandinteractions appear to involve signaling molecules similar tothose already recognized in vertebrate immunocyte signal transductionpathways, such as protein kinases A and C, focal adhesion kinase,Src, Ca²⁺ and mitogen-activated protein kinase. Overall, theexperimental evidence suggests that molluscan immune responsesrely on molecules that share homology with those of vertebratesignaling systems. As more information regarding the molecularnature of hemocyte recognition receptors and their associatedsignaling molecules is accumulated, a clearer picture of howhemocyte immune responses to invading organisms are regulatedwill begin to emerge.