Posted by: Kasra
We usually consider exiting the phagolysosome and entering the cell cytoplasm to be a immune evasion mechanism for pathogens. The pathogens inside the phagolysosome can be processed and presented via MHCII to the adaptive immune system, but once free of that compartment, the pathogen could potentially ‘hide’ from the immune system, well apparently not that much! Apart from the intracellular pattern recognition receptors (NLRs), researchers have found another receptor that responds to intracellular presence of antibodies. McEwan et al. showed that if antibody coated viruses or bacteria have entered the cytosol, presence of the Fc part of the antibody can be sensed by a protein called TRIM21. This could in turn result in an inflammatory and anti-viral response by activating NF-κB and AP-1 and production of cytokines. To me, this is an excellent example that shows how the host and the pathogens have evolved together for many years becoming more and more complex through an arms race. A newly developed strategy by one party is followed by a counter strategy by the other party.
McEwan WA, Tam JC, Watkinson RE, Bidgood SR, Mallery DL, & James LC (2013). Intracellular antibody-bound pathogens stimulate immune signaling via the Fc receptor TRIM21. Nature immunology, 14 (4), 327-36 PMID: 23455675
Geijtenbeek TB, & Gringhuis SI (2013). An inside job for antibodies: tagging pathogens for intracellular sensing. Nature immunology, 14 (4), 309-11 PMID: 23507635