Fc receptors act as innate immune receptors during infection?

Abstract

Innate immunity constitutes the first nonspecific immunological line of defense against infection. In this response, a variety of mechanisms are activated: the complement system, phagocytosis, and the inflammatory response. Then, adaptive immunity is activated. Major opsonization mediators during infections are immunoglobulins (Igs), the function of which is mediated through Fc receptors (FcRs). However, in addition to their role in adaptive immunity, FcRs have been shown to play a role in innate immunity by interacting directly with bacteria in the absence of their natural ligands (Igs). Additionally, it has been hypothesized that during the early phase of bacterial infection, FcRs play a protective role via innate immune functions mediated through direct recognition of bacteria, and as the infection progresses to later phases, FcRs exhibit their established function as receptors in adaptive immunity. This review provides detailed insight into the potential role of FcRs as innate immune mediators of the host defense against bacterial infection independent of opsonins.

Keywords: FcR; ITAM bearing receptors; bacterial clearance; infection; innate immunity.

Figure 1

Role of FcRs (FcαRI/FcγRs) in the Regulation of cellular immune responses. (A) cell activation through FcRs mediated ITAM signaling. The crosslinking of the FcαRI by an immune complex containing IgA results in Src family kinases activation (Lyn and Fyn), followed by ITAM tyrosine residues phosphorylation, that will then serve as docking sites for the tyrosine kinase Syk, triggering PI3K, PLCγ activation signaling pathways and calcium release initiating pro-inflammatory responses. In parallel, sequential phosphorylation of Src family kinases, leads to the activation of Raf-1–MEK–MAP, launching a cascade of nuclear processes including gene expression and the activation of transcription factors. (B) ITAMi induced inhibition and homeostatic control. Monovalent targeting of the FcRs activates the Src kinase, Lyn, which partially phosphorylates the tyrosine within the FcRγ chain. The phosphorylated tyrosine serves for the transient recruitment of Syk followed by the stable recruitment of phosphatase-1 (SHP-1) to the FcRγ-chain. SHP-1 coordinates the anti-inflammatory response by dephosphorylating different proteins. Adapted from (21).

Figure 2

Schematic illustration summarizing the role of FcRs (FcαRI/FcγRs) in bacterial clearance and potential contribution to innate immunity responses during infection. Left panel: FcRs serve as an innate receptor during the early phase of infection by interacting directly with bacteria, the question about the FcRs to interact directly with other pathogens, such as viruses and bacteria is maintained. Right panel: During the late phase, FcRs are involved in innate and adaptive immune responses through double interaction with opsonized bacteria (IgA, IgG and CRP) and non-opsonized bacteria. Adapted from (50).