Chapter 22 : The Role and Function of Fcγ Receptors on Myeloid Cells

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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 ( ). 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 ( ). 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 and genes provided evidence for strong positive selection pressure in human populations, and several nonsynonymous polymorphisms influencing receptor activity have been associated with disease susceptibility ( ).

Citation: Bournazos S, Wang T, Ravetch J. 2017. The Role and Function of Fcγ Receptors on Myeloid Cells, p 407-427. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0045-2016
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Figure 1

Structure and composition of the Fc-associated N-linked glycan regulates binding to type I and type II FcγRs. An N-linked glycan structure is attached at the C2 domain of each of the two heavy chains of IgG and consists of a core heptasaccharide structure that is composed of fucose, galactose, -acetylglucosamine, and sialic acid residues. The structure and composition of this Fc-associated glycan determine binding specificity and affinity of the IgG Fc domain for different types of FcγRs. Several glycoform combinations exist with distinct binding capacity to interact with type I and type II FcγRs.

Citation: Bournazos S, Wang T, Ravetch J. 2017. The Role and Function of Fcγ Receptors on Myeloid Cells, p 407-427. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0045-2016
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Image of Figure 2
Figure 2

Overview of type I and type II FcγR structure and expression pattern in myeloid cell populations. Structural characteristics of type I and type II FcγRs. Type I FcγRs belong to the Ig receptor superfamily and are composed of two or three extracellular Ig-like domains that interact with the IgG Fc domain at the hinge-proximal region of the C2 domain. Type II FcγRs comprise DC-SIGN and CD23, both C-type lectin receptors, which bind sialylated Fc IgGs. Expression pattern of type I and type II FcγRs in myeloid leukocyte populations. The expression of several FcγRs is determined by cell differentiation status and is regulated by cytokines like IL-4 and IFN-γ.

Citation: Bournazos S, Wang T, Ravetch J. 2017. The Role and Function of Fcγ Receptors on Myeloid Cells, p 407-427. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0045-2016
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Figure 3

Effector functions and processes that are regulated by Fc-FcγR interactions. Engagement of type I and type II FcγRs by the Fc domain of IgG initiates signaling cascades with diverse proinflammatory, anti-inflammatory, and immunomodulatory consequences on myeloid cells, including granulocytes, monocytes, macrophages, DCs, and platelets. ROS, reactive oxygen species.

Citation: Bournazos S, Wang T, Ravetch J. 2017. The Role and Function of Fcγ Receptors on Myeloid Cells, p 407-427. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0045-2016
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