An intracellular receptor for antibodies

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.


From Geijtenbeek TB, & Gringhuis SI (2013). An inside job for antibodies: tagging pathogens for intracellular sensing. Nature immunology, 14 (4), 309-11 PMID: 23507635

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

Parasites lead to evolution of robustness against gene loss in host signaling networks

Posted by Hamed Shateri Najafabadi

A new study by Marcel Salathé and Orkun Soyer reveals exciting evolutionary consequences of host-parasite interactions on the architecture of biological networks of the host. Their paper, which was published a few days ago in Molecular Systems Biology, is one of those that you read and wonder why no one had thought of it before! The approach that they use is elegant and the findings are very significant.

Marcel is now a postdoc fellow at Stanford and very soon is going to start working on “questions about the non-genetic (e.g. cultural) effects on disease dynamics” (I got it from his web page). I asked him to write a synopsis of his paper for The Parasite Diary, and here it is:

“Many molecular pathways are robust against removal of parts, but why such robustness is evolutionary maintained is a question that has not been answered yet. Another, seemingly unrelated finding in recent years is the process by which parasites attack their hosts and evade an immune response from the host. Evidence is accumulating that the most frequent evasion strategy of parasites is to interfere with the protein machinery of hosts, for example by suppressing important genes that are necessary to recognize a parasite and/or mount an immune response – we cite various key papers in the study.
Our idea was to bring these two observations together: if parasites interfere with host pathways, they create selective pressure on the host to avoid such interference. One obvious solution to this problem is that hosts would evolve pathways that are robust to the suppression of a protein – if a parasite suppresses the protein, the host would still be able to respond in the appropriate fashion. We believe that part of what we see in knockout studies – which are usually performed in the lab in the absence of parasites – could be explained by this phenomenon.
To see whether our idea made sense we used a mathematical model of pathway dynamics and ran evolutionary simulations in the computer. Our findings confirmed that our proposal is plausible, and in principle it is also testable. The evolved robustness resulted either from redundancy or from specific network architecture, and was more stable when it resulted from the latter; robustness based on redundancy alone was quickly lost under subsequent stabilizing evolution (without parasite interference).
Altogether, we hope that this type of research invites biologists to look closer at the ecological aspects of systems biology properties.
Parasites are an extremely strong and continuous source of selection on any species (with maybe the notable exception of viruses), and such strong selection pressures should not be ignored when we try to understand evolutionary processes.”

Thank you Marcel for your enjoyable paper. We are looking forward to your future works.