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Antibodies can fight pathogens inside cells by binding to them and recruiting TRIM21. This intracellular antibody recognition triggers immune responses, reducing viral replication and preventing severe disease.

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Area of Science:

  • Immunology
  • Cell Biology
  • Virology

Background:

  • Antibodies are key immune molecules targeting extracellular pathogens via phagocytosis and complement.
  • Pathogens like viruses evade extracellular immunity by infecting host cells.
  • Existing immune mechanisms are primarily extracellular, leaving intracellular pathogens less targeted.

Purpose of the Study:

  • To investigate the role of antibodies in intracellular immunity.
  • To understand how antibodies activate immune responses within infected cells.
  • To elucidate the function of the cytosolic antibody receptor TRIM21 in antiviral defense.

Main Methods:

  • Studying antibody-mediated pathogen entry into host cells.
  • Investigating the interaction between pathogen-bound antibodies and TRIM21.
  • Analyzing TRIM21-initiated sensor and effector responses.
  • Utilizing mouse models to assess the in vivo importance of TRIM21.

Main Results:

  • Pathogen-bound antibodies are internalized into host cells.
  • The cytosolic receptor TRIM21 binds to internalized antibodies.
  • TRIM21 triggers intracellular sensor and effector pathways reducing viral replication.
  • TRIM21 deficiency leads to uncontrolled viral spread and mortality in mice.

Conclusions:

  • Antibodies mediate intracellular immunity by engaging TRIM21.
  • TRIM21 is crucial for antiviral defense against intracellular pathogens.
  • Targeting intracellular antibody-mediated immunity offers new therapeutic strategies.