Intracellular Innate Immunity of Antibodies

A special issue of Antibodies (ISSN 2073-4468).

Deadline for manuscript submissions: closed (30 June 2017) | Viewed by 18949

Special Issue Editor


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Guest Editor
SRI International Biosciences Division, Cancer and Metabolism Center, #100-51, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA
Interests: study of B-cell response to tumors and B-cell interactions with innate immunity in the tumor microenvironment; development and evaluation of affinity reagents for diagnostic and targeted-imaging of cancer and therapy for ovarian cancer

Special Issue Information

Dear Colleagues,

The immune system provides critical protection against pathogens, both through the adaptive immune system, which is highly specific and endowed of memory but slow to develop on first exposure, and the innate immune system, which can immediately sense any intracellular pathogens through the recognition of molecular patterns associated with pathogens (PAMPs) or damaged cells (DAMPs, danger signals, or alarmins) by germline-encoded pattern recognition receptors (PRRs). Cell single sensing can elicit multiple immune responses to efficiently reduce spreading infection. Adaptive immune responses are carried out by activated B and T cells, which produce antigen-specific antibodies or cytotoxic T cells, respectively. Antibodies that patrol the extracellular spaces bind to pathogens, which directly inactivate pathogen functions or prime them for destruction by complement (complement-dependent cytotoxicity, CDC) or phagocytosis (antibody-dependent cell-mediated cytotoxicity, ADCC). In addition to these mechanisms, antibodies also activate intracellular innate immunity when they are carried in the cell during pathogen entry. Once in the cell, pathogen-attached antibodies bind to a cytosolic antibody receptor (Tripartite motif-containing 21, TRIM21) that mediates antibody-dependent intracellular neutralization (ADIN). While ADIN has only been observed to act against adenovirus thus far, it is likely to also be effective against other pathogens. This Special Issue of Antibodies focuses on intracellular innate immunity of antibodies, with specific emphasis on different pathogenic mechanisms, potential therapeutic options and critical information that can be derived from the study of intracellular innate immunity.

Dr. Nathalie Scholler
Guest Editor

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Keywords

  • PAMPs
  • DAMPs
  • PRR
  • TRIM21
  • ADIN
  • RIG-I
  • MDA5 NF-κB
  • AP-1 and IRF signaling pathways

 

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Published Papers (2 papers)

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Review

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Review
Surveillance for Intracellular Antibody by Cytosolic Fc Receptor TRIM21
by William A. McEwan
Antibodies 2016, 5(4), 21; https://doi.org/10.3390/antib5040021 - 2 Nov 2016
Cited by 12 | Viewed by 11847
Abstract
TRIM21 has emerged as an atypical Fc receptor that is broadly conserved and widely expressed in the cytoplasm of mammalian cells. Viruses that traffic surface-bound antibodies into the cell during infection recruit TRIM21 via a high affinity interaction between Fc and TRIM21 PRYSPRY [...] Read more.
TRIM21 has emerged as an atypical Fc receptor that is broadly conserved and widely expressed in the cytoplasm of mammalian cells. Viruses that traffic surface-bound antibodies into the cell during infection recruit TRIM21 via a high affinity interaction between Fc and TRIM21 PRYSPRY domain. Following binding of intracellular antibody, TRIM21 acts as both antiviral effector and sensor for innate immune signalling. These activities serve to reduce viral replication by orders of magnitude in vitro and contribute to host survival during in vivo infection. Neutralization occurs rapidly after detection and requires the activity of the ubiquitin-proteasome system. The microbial targets of this arm of intracellular immunity are still being identified: TRIM21 activity has been reported following infection by several non-enveloped viruses and intracellular bacteria. These findings extend the sphere of influence of antibodies to the intracellular domain and have broad implications for immunity. TRIM21 has been implicated in the chronic auto-immune condition systemic lupus erythematosus and is itself an auto-antigen in Sjögren’s syndrome. This review summarises our current understanding of TRIM21’s role as a cytosolic Fc receptor and briefly discusses pathological circumstances where intracellular antibodies have been described, or are hypothesized to occur, and may benefit from further investigations of the role of TRIM21. Full article
(This article belongs to the Special Issue Intracellular Innate Immunity of Antibodies)
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733 KiB  
Review
Epigenetic Regulation of Innate Immunity by microRNAs
by Chandra S. Boosani and Devendra K. Agrawal
Antibodies 2016, 5(2), 8; https://doi.org/10.3390/antib5020008 - 1 Apr 2016
Cited by 13 | Viewed by 6605
Abstract
The innate immune response, which is usually referred to as the first line of defense, protects the hosts against pathogenic micro-organisms. Some of the biomolecules released from the pathogens, such as proteins, lipoproteins and nucleic acids, which are collectively termed as pathogen-associated molecular [...] Read more.
The innate immune response, which is usually referred to as the first line of defense, protects the hosts against pathogenic micro-organisms. Some of the biomolecules released from the pathogens, such as proteins, lipoproteins and nucleic acids, which are collectively termed as pathogen-associated molecular patterns (PAMPs), elicit signaling mechanisms that trigger immune responses in the hosts. Pathogen recognition receptors (PRRs) on the host cells recognize these PAMPs and initiate intracellular signaling through toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and other pathways which induce production of pro-inflammatory cytokines and type I interferons. Recently, different members of tripartite motif containing proteins (TRIM) family of proteins were identified to intercept and regulate these cellular pathways. Specific targets of TRIM proteins have been identified and their molecular mechanisms were unraveled and identified unique domains involved in protein-protein interactions. Though innate immunity represents a tight and well conserved immune system in the host, gene expression in innate immunity was identified to be influenced by several epigenetic mechanisms including regulation by microRNAs (miRNAs). In this review, we present critical analysis of the findings on the identification of specific miRNAs that modulate expression of target genes involved in the regulation of innate immunity. Full article
(This article belongs to the Special Issue Intracellular Innate Immunity of Antibodies)
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