Antibodies, which are known to patrol the extracellular space in the body and bind to pathogens such as bacteria and viruses, can also trigger sensors inside cells that lead to the activation of the immune system, according to a paper published this week online in Nature Immunology. A better understanding of these signaling pathways may have important implications for development of vaccination strategies.
Antibodies can be carried into the cell during pathogen infection where they are detected by a ubiquitously expressed intracellular antibody receptor called TRIM21. William McEwan and colleagues show that in mice and humans, TRIM21 recognition of intracellular antibodies activates immune signaling, resulting in production of pro-inflammatory cytokine production and the induction of an antiviral state as a result of the immune response. Antibody sensing by TRIM21 can be stimulated upon infection by DNA or RNA viruses or intracellular bacteria, suggesting it functions as an immune activation pathway independent of pattern recognition receptors specific for various pathogen molecular signatures.