The Role and Function of Fcγ Receptors on Myeloid Cells

A key determinant for the survival of an organism is the ability to recognize and respond to invading pathogens without damaging host tissues. This is accomplished largely by the concerted activity of the innate and adaptive branches of the immune system, which efficiently eliminate invading pathogens and restore tissue homeostasis. An initial step in the generation of robust immune responses is the recognition of pathogens by host cells, triggering subsequent immune cell activation and induction of proinflammatory responses. This initial recognition is facilitated via pathogen-associated molecular patterns (PAMPs) that represent highly conserved molecular structures uniquely found in bacterial, viral, and fungal pathogens but not in host tissues. Such structures include peptidoglycans, zymosan, lipopolysaccharides, flagellin, double-stranded and single-stranded RNA, and CpG-containing DNA (1). So far, an ever increasing number of receptors with the capacity to sense and respond to these PAMPs have been identified and are broadly categorized into distinct receptor families: Toll-like receptors (TLRs), RIG-I (retinoic acid-inducible gene I)-like receptors, NOD-like receptors, and C-type lectin receptors (2–4). Following engagement, these pattern recognition receptors trigger the activation of several inflammatory pathways essential to mediate robust antimicrobial activity and induce sustained immune responses. This central role in immunity for pathogen sensing by innate immune receptors is also reflected by the emergence of pattern recognition receptors early in evolutionary history, as evidenced by the presence of highly conserved gene orthologs in invertebrate species. Additionally, genetic analysis of human TLR and NOD genes provided evidence for strong positive selection pressure in human populations, and several nonsynonymous polymorphisms influencing receptor activity have been associated with disease susceptibility (1).