**2.4 Antibody opsonization**

Emerging data suggest a potential role for opsonin-mediated phagocytosis in nonmyeloid cells [87–93]. Classical membrane-bound Fcγ receptors, namely FcγRI, FcγRII, and FcγRIII, and their capacity to recognize immunoglobulins are more typically associated with myeloid cell-based professional phagocytosis [57]. A more poorly understood, and somewhat atypical, class of immunoglobulin receptor, known as the neonatal Fc receptor (FcRn), is expressed ubiquitously throughout multiple tissue types, including pulmonary epithelium [92], intestinal epithelium [87], microvascular endothelium [91], and the placenta [89]. It was initially thought that FcRn is expressed in fetal and neonatal tissues; however, it has since been demonstrated that expression is sustained throughout life [90]. The FcRn has a strong affinity for albumin [90] and IgG antibodies [88]. IgG-mediated phagocytosis *via* FcRn has been noted in myeloid cells [93], but evidence for phagocytosis in nonmyeloid cells *via* this receptor is lacking. FcRn expression in nonmyeloid cells appears to be intracellular, thus lacking the capacity for extracellular surveillance [94]. Instead, it is thought that the primary function for FcRn is transcytosis of IgGs across endothelial and epithelial membranes, as opposed to opsonin-mediated phagocytosis. The fundamental machinery is, however, present in nonmyeloid tissues and models have even been proposed based on studies demonstrating IgG-mediated phagocytosis of extracellular myelin debris [7, 47].

#### **Figure 2.**

*Phagosome maturation. Phagosome maturation in nonmyeloid cells is like that of professional phagocytes, however less efficient. The phagocytosis process is outlined as; 1) internalization, resulting in the formation of the early phagosome, recruiting components such as Rab5 and EEA1. 2) Phagosome maturation, where Rab5 is replaced with Rab7 and factors such as RILP and LAMP 1 are recruited. 3) Lysosomal fusion, releasing factors such as degradation enzymes within the phagosome, which can result in pathogen killing and recycling of degraded products. This figure was created with BioRender.com.*
