Inside-Out Control of Fc-Receptors

Koenderman, Leo

doi:10.3389/fimmu.2019.00544

Cited by 41 publications

(46 citation statements)

References 102 publications

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“…It is feasible that upon activation with immune complexes, macrophage FcRs may pair with different membrane proteins. Cell surface receptor interactions and crosstalk between signaling pathways might represent important regulatory mechanisms (Rittirsch et al, 2009;van Egmond et al, 2015;Koenderman, 2019), influencing parasite entry into the cell.…”

Section: Discussionmentioning

confidence: 99%

Prolyl Oligopeptidase From Leishmania infantum: Biochemical Characterization and Involvement in Macrophage Infection

et al. 2020

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Leishmania infantum is a flagellated protozoan and one of the main causative agents of visceral leishmaniasis. This disease usually affects the human reticuloendothelial system, can cause death and available therapies may lead to serious side effects. Since it is a neglected tropical disease, the incentives for the development of new drugs are insufficient. It is important to know Leishmania virulence factors that contribute most to the disease in order to develop drugs. In the present work, we have produced L. infantum prolyl oligopeptidase (rPOPLi) in Escherichia coli, and investigated its biochemical properties as well as the effect of POP inhibitors on its enzymatic activity and on the inhibition of the macrophage infection by L. infantum. The optimal activity occurred at pH 7.5 and 37 • C in the presence of DTT, the latter increased rPOPLi catalytic efficiency 5-fold on the substrate N-Suc-Gly-Pro-Leu-Gly-Pro-AMC. The enzyme was inhibited by TPCK, TLCK and by two POP specific inhibitors, Z-Pro-prolinal (ZPP, IC 50 4.2 nM) and S17092 (IC 50 3.5 nM). Besides being a cytoplasmic enzyme, POPLi is also found in punctuate structures within the parasite cytoplasm or associated with the parasite plasma membrane in amastigotes and promastigotes, respectively. Interestingly, S17092 and ZPP prevented parasite invasion in murine macrophages, supporting the involvement of POPLi in the invasive process of L. infantum. These data suggest POPLi as a virulence factor that offers potential as a target for designing new antileishmanial drugs.

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Section: Discussionmentioning

confidence: 99%

Prolyl Oligopeptidase From Leishmania infantum: Biochemical Characterization and Involvement in Macrophage Infection

et al. 2020

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“…Can be divided into inhibitory (FcγRIIB) and activating receptors (FcγRI, FcγRIIA, FcγRIIC, FcγRIIIA, and FcγRIIIB). Through binding of IgG via the Fc portion, FcγRs are essential for regulating responses to infections and controlling inflammation (8, 9).…”

Section: Introductionmentioning

confidence: 99%

The Neonatal Fc Receptor (FcRn): A Misnomer?

et al. 2019

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Antibodies are essential components of an adaptive immune response. Immunoglobulin G (IgG) is the most common type of antibody found in circulation and extracellular fluids. Although IgG alone can directly protect the body from infection through the activities of its antigen binding region, the majority of IgG immune functions are mediated via proteins and receptors expressed by specialized cell subsets that bind to the fragment crystallizable (Fc) region of IgG. Fc gamma (γ) receptors (FcγR) belong to a broad family of proteins that presently include classical membrane-bound surface receptors as well as atypical intracellular receptors and cytoplasmic glycoproteins. Among the atypical FcγRs, the neonatal Fc receptor (FcRn) has increasingly gained notoriety given its intimate influence on IgG biology and its ability to also bind to albumin. FcRn functions as a recycling or transcytosis receptor that is responsible for maintaining IgG and albumin in the circulation, and bidirectionally transporting these two ligands across polarized cellular barriers. More recently, it has been appreciated that FcRn acts as an immune receptor by interacting with and facilitating antigen presentation of peptides derived from IgG immune complexes (IC). Here we review FcRn biology and focus on newer advances including how emerging FcRn-targeted therapies may affect the immune responses to IgG and IgG IC.

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“…Perhaps, but it could be noticed that some mutations suppressing the inhibitor receptor have been associated with increasing macrophage phagocytosis of Plasmodium (42). Moreover, the mechanism called "insideout control" and well reviewed by Koenderman et al (43) could may be explained how FcgRIIB apparently in low number succeed to inhibit FcgRIIA's activity. Indeed, by modulating the affinity, i.e., the strength of the receptor for its ligand, modulating the valency or the engagement of multiple receptors, modulating the interaction with the signal chains, the other receptors, or their localization in the various membranes, it is possible to regulate the function of the receptors.…”

Section: The Structure and Function Of Fc Gamma Receptorsmentioning

confidence: 99%

“…The expression of the FcgRIIIA receptor has been indicated to be influenced by the glycosylation. The review by Koenderman et al (43) mentioned that an ectopically expressing tail-less version of FcgRIIB could weaken the signal response. Again, some studies have shown that a mutation in FCGR2C genes to a stop codon leads to the expression of FcgRIIB in NK cells with consequences of inhibiting its function (34,48).…”

Section: The Structure and Function Of Fc Gamma Receptorsmentioning

confidence: 99%

Polymorphisms in Fc Gamma Receptors and Susceptibility to Malaria in an Endemic Population

et al. 2020

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Repeated infections by Plasmodium falciparum result in a humoral response that could reduce disease symptoms and prevent the development of clinical malaria. The principal mechanism underlying this humoral response is that immunoglobulin G (IgG) binds directly to the parasites, thus causing their neutralization. However, the action of antibodies alone is not always sufficient to eliminate pathogens from an organism. One key element involved in the recognition of IgG that plays a crucial role in the destruction of the parasites responsible for spreading malaria is the family of Fc gamma receptors. These receptors are expressed on the surface of immune cells. Several polymorphisms have been detected in the genes encoding these receptors, associated with susceptibility or resistance to malaria in different populations. In this review, we describe identified polymorphisms within the family of Fc gamma receptors and the impact of these variations on the response of a host to infection as well as provide new perspectives for the design of an effective vaccine for malaria.

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Inside-Out Control of Fc-Receptors

Cited by 41 publications

References 102 publications

Prolyl Oligopeptidase From Leishmania infantum: Biochemical Characterization and Involvement in Macrophage Infection

Prolyl Oligopeptidase From Leishmania infantum: Biochemical Characterization and Involvement in Macrophage Infection

The Neonatal Fc Receptor (FcRn): A Misnomer?

Polymorphisms in Fc Gamma Receptors and Susceptibility to Malaria in an Endemic Population

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