Tissues: the unexplored frontier of antibody mediated immunity

Webb, Nicholas E.; Bernshtein, Biana; Alter, Galit

doi:10.1016/j.coviro.2021.01.001

Cited by 23 publications

(11 citation statements)

References 190 publications

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“…Although the up-regulation of Fc receptor expression in male placentas may represent a compensatory placental response driven by reduced maternal antibody titer and transplacental transfer of SARS-CoV-2 antibodies (22,102,103), this response was likely reinforced by the increased IFN signaling in males versus females. IFN-stimulated signaling may affect placental antibody transfer via alteration in Fc receptor expression and function (104)(105)(106); for example, type I IFN signaling is known to up-regulate Fc receptor expression on monocytes (107).…”

Section: Discussionmentioning

confidence: 99%

Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses

et al. 2021

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Section: Discussionmentioning

confidence: 99%

Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses

et al. 2021

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“…However, except for blocking infections, antibodies may have other meaningful functions to the host. It might work in collaboration with cells of the immune system for a more effective protest against pathogens or contribute to the immunity with different unknown mechanisms [44, 45]. Therefore, a high anti-VZV IgG level may also indicate a healthy immune function.…”

Section: Discussionmentioning

confidence: 99%

Exploring the possible causal role of the immune response to varicella-zoster virus on multiple traits: a phenome-wide Mendelian randomization study

Lophatananon

Mekli

et al. 2022

Preprint

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Background The immune response to infections could be largely driven by the individuals genes, especially in the major histocompatibility complex (MHC) region. Varicella-zoster virus (VZV) is a highly communicable pathogen. In addition to infection, the re-activations of VZV can be a potential causal factor for multiple traits. Identification of VZV immune response-related health conditions can therefore help elucidate the aetiology of certain diseases. Methods A phenome-wide Mendelian randomization study (MR-PheWAS) of anti-VZV Immunoglobulin G (IgG) level with 1,370 traits was conducted to explore the potential causal role of VZV-specific immunity on multiple traits using the UK Biobank cohort. For each trait, we performed Mendelian randomization (MR) analyses using five methods with or without instrumental variables (IVs) in the MHC region. Results We identified 49 single nucleotide polymorphisms (SNPs) associated with anti-VZV IgG level as IVs, five of which were located in the MHC region. Statistical evidence for a causal effect of anti-VZV IgG level on 75 traits was found in at least three of the MR methods, 60 traits if IVs in the MHC region were removed from MR analysis. With or without the MHC IVs, we found that a higher anti-VZV IgG level led to increased risk of 14 diseases and lower risks of 9 diseases. In addition, anti-VZV IgG level was causally associated with 5 biomarker-related traits. Conclusions Anti-VZV IgG was causally associated with multiple traits. MHC IVs had a substantial impact on MR causal inference, and therefore, should not be neglected from analysis.

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“…In the case of a pathogen-specific nano-vaccine, the candidate antigen would be a pathogen-specific surface protein in order to induce neutralizing antibodies [79]. Alternatively (or in addition), a pathogen-derived protein, which would be apparent on the surface of infected cells [80], would be a suitable antigen, inducing the production of antibodies that recognize infected cells, and trigger classical complement activation [81] or antibody-dependent cytotoxicity [82]. A nano-vaccine applied for tumor therapy should be decorated with a tumor-associated/specific surface protein in order to obtain antibodies that recognize malignant cells and confer antibodymediated cytotoxic effects [83,84].…”

Section: Discussionmentioning

confidence: 99%

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

Bednarczyk

Medina‐Montano

Fittler

et al. 2021

IJMS

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The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses.

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Tissues: the unexplored frontier of antibody mediated immunity

Cited by 23 publications

References 190 publications

Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses

Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses

Exploring the possible causal role of the immune response to varicella-zoster virus on multiple traits: a phenome-wide Mendelian randomization study

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

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