Recognition diversity and effector mechanisms of immunoglobulin superfamily proteins in invertebrates.

Traditionally, highly specific immune responses are considered to rely on the vertebrate adaptive immune system centered on immunoglobulins, while invertebrates defend themselves solely through innate immunity. Nevertheless, accumulating studies have demonstrated that diverse immunoglobulin superfamily (IgSF) proteins play indispensable roles in the recognition and defense against pathogenic invasion in invertebrates. This review systematically summarizes the latest advances in the specific recognition mediated by IgSF proteins via diversified mechanisms, with a focus on the generation of tens of thousands of isoforms through alternative splicing of Drosophila Down syndrome cell adhesion molecule (Dscam) for recognizing distinct pathogens, as well as the anti-parasitic immune strategies of mollusk Fibrinogen-related proteins (FREPs) mediated by gene family expansion and somatic mutation. In terms of signal transduction, this article analyzes how IgSF receptors such as CgIgIT recruit phosphatases via intracellular domains, thereby regulating core signaling pathways including MAPK to maintain immune homeostasis. Furthermore, regarding the scientific issue of whether immune memory exists in invertebrates, we discuss the potential and challenges of IgSF proteins as candidate molecules mediating immune priming or specific immune memory in invertebrates. Although the functional framework of IgSF proteins in pathogen recognition and signal transduction has been preliminarily established, biophysical quantitative data on their interactions with specific ligands remain extremely scarce, which represents a critical direction for future research to unravel the molecular mechanisms underlying invertebrate immune recognition.