Immunoglobulin-like receptors and the generation of innate immune memory

Host immunity is classically divided into “innate” and “adaptive.” While the former has always been regarded as the first, rapid, and antigen-nonspecific reaction to invading pathogens, the latter represents the more sophisticated and antigen-specific response that has the potential to persist and generate memory. Recent work however has challenged this dogma, where murine studies have successfully demonstrated the ability of innate immune cells (monocytes and macrophages) to acquire antigen-specific memory to allogeneic major histocompatibility complex (MHC) molecules. The immunoreceptors so far identified that mediate innate immune memory are the paired immunoglobulin-like receptors (PIRs) in mice, which are orthologous to human leukocyte immunoglobulin-like receptors (LILRs). These receptor families are mainly expressed by the myelomonocytic cell lineage, suggesting an important role in the innate immune response. In this review, we will discuss the role of immunoglobulin-like receptors in the development of innate immune memory across species.