“The cell is effectively disguising itself as an infectious agent,” Kagan said. “The result is that he convinces himself that he is infected and then acts as such.”
Immune responses can be destructive, and especially antiviral responses. Because viruses are most dangerous when they are already inside a cell, most immune strategies that attack viral infections work in part by damaging and killing infected cells.
That’s why cells shout “Virus!” At your own risk. In most tissues, Alu sequences are highly suppressed, so they never have the opportunity to mimic a viral attack. And yet, that is the exact scenario that the placenta seems to create on purpose. How do you balance the health of the growing embryo with a potentially risky immune response?
In experiments with mice, Totary-Jain’s team found that double-stranded RNAs from the placenta and the resulting immune response did not appear to harm developing embryos. Instead, they protected the embryos from Zika virus infection. The placental cells were able to toe the line (conferring protection to the embryos without provoking a self-destructive immune response) because they resorted to the milder defenses of interferon lambda.
Typically, the first responders to double-stranded Alu RNA leaks are type I and type II interferons, which rapidly recruit destructive immune cells to the site of an infection, leading to tissue damage and even autoimmune diseases. Interferon lambda, on the other hand, is a type III interferon. It acts locally by communicating only with the cells within the tissue, generating a milder immune response, which can be maintained long-term in the placenta.
It remains a mystery how placental cells manage to activate only interferon lambda, keeping the immune response simmering but without overflowing. But Totary-Jain has an idea why placental cells evolved this trick that other cells apparently avoid: Since the placenta is discarded at birth, perhaps it can afford to take immunological risks that other tissues cannot.
The findings reveal a new strategy that the placenta has to protect the fetus, in addition to the mother’s immune system. Since the mother’s immune response is weakened during pregnancy to prevent attacks on genetically distinct embryonic cells, the placenta has had to develop additional defenses for the growing baby it supports.
However, this trick (a low-level immune response generated by a fake virus) may not be limited to the placenta. Researchers at Columbia University recently described a similar phenomenon in neurons. They observed RNA from different genomic elements Joined in double strands to produce an immune response. In this case, the immune system requested a more destructive type I interferon, but it was produced at low levels. The authors hypothesized that chronic low-level inflammation in the brain may keep infections under control, preventing significant inflammation and neuronal death.
It’s possible, then, that this type of immune deception is more common than anyone thought. By studying how the immune system appears to break its own rules, scientists can better define what the rules are in the first place.
original story reprinted with permission of Quanta Magazine, an editorially independent publication of the Simons Foundation whose mission is to improve public understanding of science by covering developments and trends in research in mathematics and the physical and biological sciences.