Differences in endocytosis mediated by FcγRIIA and FcγRIIB2

Zhang, Christine Y.; Booth, James W.

doi:10.1016/j.molimm.2011.09.003

Cited by 9 publications

(16 citation statements)

References 34 publications

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“…However, the relationship between internalization of immune complexes and ADE of infection by SARS-CoV via FcγRIIs appears to be a complex process. Thus, FcγRIIB2 has been shown to mediate internalization of immune complexes at a faster rate than FcγRIIA [33], whereas we found that ADE of infection via FcγRIIA was more prominent than with FcγRIIB. Recently, involvement of downstream signaling triggered by FcγRs activation has been evaluated with respect to ADE of dengue virus infection [34].…”

Section: Discussioncontrasting

confidence: 52%

Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus

Yip

Leung

Cheung

et al. 2014

Virol J

238

224

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BackgroundPublic health risks associated to infection by human coronaviruses remain considerable and vaccination is a key option for preventing the resurgence of severe acute respiratory syndrome coronavirus (SARS-CoV). We have previously reported that antibodies elicited by a SARS-CoV vaccine candidate based on recombinant, full-length SARS-CoV Spike-protein trimers, trigger infection of immune cell lines. These observations prompted us to investigate the molecular mechanisms and responses to antibody-mediated infection in human macrophages.MethodsWe have used primary human immune cells to evaluate their susceptibility to infection by SARS-CoV in the presence of anti-Spike antibodies. Fluorescence microscopy and real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) were utilized to assess occurrence and consequences of infection. To gain insight into the underlying molecular mechanism, we performed mutational analysis with a series of truncated and chimeric constructs of fragment crystallizable γ receptors (FcγR), which bind antibody-coated pathogens.ResultsWe show here that anti-Spike immune serum increased infection of human monocyte-derived macrophages by replication-competent SARS-CoV as well as Spike-pseudotyped lentiviral particles (SARS-CoVpp). Macrophages infected with SARS-CoV, however, did not support productive replication of the virus. Purified anti-viral IgGs, but not other soluble factor(s) from heat-inactivated mouse immune serum, were sufficient to enhance infection. Antibody-mediated infection was dependent on signaling-competent members of the human FcγRII family, which were shown to confer susceptibility to otherwise naïve ST486 cells, as binding of immune complexes to cell surface FcγRII was necessary but not sufficient to trigger antibody-dependent enhancement (ADE) of infection. Furthermore, only FcγRII with intact cytoplasmic signaling domains were competent to sustain ADE of SARS-CoVpp infection, thus providing additional information on the role of downstream signaling by FcγRII.ConclusionsThese results demonstrate that human macrophages can be infected by SARS-CoV as a result of IgG-mediated ADE and indicate that this infection route requires signaling pathways activated downstream of binding to FcγRII receptors.

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Section: Discussioncontrasting

confidence: 52%

Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus

Yip

Leung

Cheung

et al. 2014

Virol J

238

224

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“…Coengagement of Fc␥RIIB with activating Fc␥Rs by RTX inhibits tumor killing [15]. However, Fc␥RIIB is known to efficiently internalize immune complexes via clathrin-dependent endocytic mechanisms [28,29]. Our in vitro data with NOTAM macrophages suggest that Fc␥R ITAM signaling may not be essentially required for trogocytosis of CD20.…”

Section: Discussionmentioning

confidence: 83%

Both activating and inhibitory Fc gamma receptors mediate rituximab-induced trogocytosis of CD20 in mice

et al. 2012

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“…The presence of intraneuronal A␤ precedes the buildup of extracellular amyloid plaques in individuals with mild cognitive impairment and AD (LaFerla et al, 2007). In many AD mouse models, intraneuronal A␤ strongly correlates with the onset of memory impairment, sometimes even without extracellular A␤ load (Billings et al, 2005;Tomiyama et al, 2010;Eimer and Vassar, 2013). Moreover, AD-like neuronal defects are ame-liorated by the modulation of intraneuronal A␤-degrading enzymes, such as neprilysin, endothelin-converting enzymes, and nuclear inclusion a (NIa) (Marr et al, 2003;Pacheco-Quinto and Eckman, 2013;Shin et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…A␤ is generated by a sequential cleavage of APP by ␤-secretase 1 and ␥-secretase complex along the endocytic pathway (Haass et al, 2012). Most cleaved A␤ in the lumen of endocytic compartments is secreted extracellularly and this event is regulated by neuronal activity (Cirrito et al, 2008;Tampellini et al, 2009;Moghekar et al, 2011). Thus, a substantial portion of intraneuronal A␤ is from the re-uptake of secreted A␤.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, a substantial portion of intraneuronal A␤ is from the re-uptake of secreted A␤. Though a group of membrane proteins in neurons have been suggested to be a receptor of A␤ so far, receptor for advanced glycation end product (RAGE), low-density lipoprotein receptor-related protein 1 (LRP1), p75 neurotrophin receptor (p75 NTR ), and ␣7 nicotinic acetylcholine receptor (␣7nAChR) were investigated to mediate neuronal uptake of A␤ (Takuma et al, 2009;Ovsepian and Herms, 2013;Kanekiyo and Bu, 2014;Yang et al, 2014). However, the pathologic impact of RAGE is not only attributed to its neuronal expression since microglial and vascular RAGE also function during disease progression (Cai et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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TOM1 Regulates Neuronal Accumulation of Amyloid-β Oligomers by FcγRIIb2 Variant in Alzheimer's Disease

et al. 2018

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Emerging evidences suggest that intraneuronal Aβ correlates with the onset of Alzheimer's disease (AD) and highly contributes to neurodegeneration. However, critical mediator responsible for Aβ uptake in AD pathology needs to be clarified. Here, we report that FcγRIIb2, a variant of Fcγ-receptor IIb (FcγRIIb), functions in neuronal uptake of pathogenic Aβ. Cellular accumulation of oligomeric Aβ not monomeric Aβ or oligomeric Aβ, was blocked by knock-out in neurons and partially in astrocytes. Aβ internalization was FcγRIIb2 di-leucine motif-dependent and attenuated by TOM1, a FcγRIIb2-binding protein that repressed the receptor recycling. TOM1 expression was downregulated in the hippocampus of male 3xTg-AD mice and AD patients, and regulated by miR-126-3p in neuronal cells after exposure to Aβ In addition, memory impairments in male 3xTg-AD mice were rescued by the lentiviral administration of TOM1 gene. Augmented Aβ uptake into lysosome caused its accumulation in cytoplasm and mitochondria. Moreover, neuronal accumulation of Aβ in both sexes of 3xTg-AD mice and memory deficits in male 3xTg-AD mice were ameliorated by forebrain-specific expression of Aβ-uptake-defective mutant. Our findings suggest that FcγRIIb2 is essential for neuropathic uptake of Aβ in AD. Accumulating evidences suggest that intraneuronal Aβ is found in the early step of AD brain and is implicated in the pathogenesis of AD. However, the critical mediator involved in these processes is uncertain. Here, we describe that the FcγRIIb2 variant is responsible for both neuronal uptake and intraneuronal distribution of pathogenic Aβ linked to memory deficits in AD mice, showing a pathologic significance of the internalized Aβ. Further, Aβ internalization is attenuated by TOM1, a novel FcγRIIb2-binding protein. Together, we provide a molecular mechanism responsible for neuronal uptake of pathogenic Aβ found in AD.

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Differences in endocytosis mediated by FcγRIIA and FcγRIIB2

Cited by 9 publications

References 34 publications

Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus

Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus

Both activating and inhibitory Fc gamma receptors mediate rituximab-induced trogocytosis of CD20 in mice

TOM1 Regulates Neuronal Accumulation of Amyloid-β Oligomers by FcγRIIb2 Variant in Alzheimer's Disease

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