Worms’ Molecular Mimicry Infiltrates Enemy Lines and Eventually Our Bloodstream

Every minute of every day there are billions of intricate acts of origami happening right under your nose. While they’re nowhere near as fun to look at as thousands of paper swans or a startlingly attractive contortionist, they are much more important to your survival.

I'm sorry, what was I talking about again?

I’m sorry, what was I talking about again?

I’m speaking, of course, of the countless configurations that proteins shape themselves into within living organisms. As a refresher, or initial course if you were too distracted by the cute girl in the front row of biology class to pay attention, proteins are made up of one or more strings of amino acids, each playing a separate and necessary biological role. But besides what they’re made of, perhaps the most critical characteristic of proteins is the way in which they are folded. The precise shapes that they take determine the receptors they will latch onto and the effects they will have on everything from genes to entire cells.

In fact, protein folding is so crucial to your existence that just a minor flaw can have major consequences. Parkinson’s disease, for example, is thought to spread from once cell to the next by a misfolded protein that passes between neurons. And we all know where Parkinson’s disease will land you.

Not quite as impressive but still fun to look at.

Not quite as impressive but still fun to look at.

On your ass.

To make matters more complicated, many proteins can be folded into different configurations, with each shape playing a different role within the body. What’s more, determining the shape of a protein is no simple matter. While computer programs have been developed that do an okay job trying to figure out different contortions, the human brain is unrivaled at the ingenuity required to truly make advancements in the most difficult puzzles. If you want to take a crack at it, you can download and play FoldIt, a game created by scientists to harness the brilliant procrastinations of puzzle solvers everywhere that has already shown fantastic results.

Screenshot from the game FoldIt.

Screenshot from the game FoldIt.

One of the more important roles that the specific shapes of proteins play is in the immune system. Every one of your native bits and pieces has a distinctive set of proteins that marks it as part of your own self. This set of proteins is called the major histocompatibility complex, or MHC for short. In contrast, objects foreign to your body – such as viruses, bacteria, fungi, hamsters, and other invaders – have different surface proteins. It is this variation that is picked up by your immune system, recognizing potential pathogens for annihilation.

There are many techniques nature has devised to get around an organism’s identification process. Superantigens activate a ton of your immune system’s soldiers, causing a massive response that attacks a lot more than just pathogens, destroying your immune system’s specificity. Other diseases, such as HIV/AIDS, attacks the cells responsible for picking out the foreign proteins and programming your body’s local Rambos.

How I like to envision my own white blood cells, T cells, etc.

How I like to envision my own white blood cells, T cells, etc.

But perhaps the most fiendishly clever way of avoiding detection is by mimicking a body’s own MHC. According to recent research from the University of Wisconsin, there’s at least one pathogen that’s managed to figure out this trick – the lowly blood fluke. And though the trick doesn’t really apply to the human immune system – it’s a way to evade the defenses of snails – it has plenty of implications for world health.

After hitching a ride inside a snail, blood flukes do eventually infect humans. Take its close relative the hookworm, for example. Walking barefooted near makeshift hole-in-the-ground toilets is a sure-fire way to pick up these cute little critters that cause anemia, weight loss, fatigue, and impaired mental function. It was hookworms that bogged down the American South’s economy back in the postbellum age. As the blog Body Horrors puts it, “The popular image during the American Civil War of the lazy Southern redneck with ‘sallow skin, bare feet, scrawny neck, protuberant abdomen, retarded intelligence, and shiftless habits’ undoubtedly derived from endemic hookworm infection and its debilitating symptoms.’”

Thanks to a massive health campaign by the Rockefeller Foundation, the problem was solved and the hookworm mostly eradicated from American soil. But it and its cousins are still alive and well in the third-world areas of the planet, causing more than 20 million infections every year.

The charming blood fluke.

The charming blood fluke.

The blood fluke’s life cycle – pretty much all varieties – begins with snails. Tiny larvae float along in bodies of water until they come across unsuspecting (likely due to their lack of higher functioning brains) slimy snails. If science could somehow figure out a way to get snails to become intolerant hosts, they could perhaps stop blood flukes in their path.

The recent study shows that at least one species of snail is immune to the infection. But what’s more, it also reveals the reason. A snail’s immune system latches onto certain carbohydrates – certain sugars – that are chemically linked to glycoproteins expressed at the larval surface or spewed out by the parasite when transforming into its next stage of development. One species of snail that is chronically infected with blood flukes produces a lot of these same carbohydrates naturally. The second species that destroys the blood flukes on sight does not.

Thus, it appears that the blood flukes have evolved a way around the snail’s natural defenses. By producing substances that mimic what the snail’s immune system is already used to ignoring, it avoids detection. In contrast, the snails that don’t produce this substance recognize it as a foreign invader and immediately release the hounds.

I bet you'd wish I'd go back to contortionists right about now, eh?

I bet you’d wish I’d go back to contortionists right about now, eh?

The researchers hope that this line of research may lead to a way to prevent blood flukes from gaining footholds in human populations. While there are effective drugs already in existence, they wear off after a year, and supplying entire populations with a constant supply of them is not economically feasible. Plus, the parasites are already evolving resistance to existing defenses.

If scientists could change the expression of the snails’ genes to produce lower amounts of the glycoproteins, their immune systems might respond better to the blood flukes. Alternatively, if they could get the blood flukes to secrete different types of glycoproteins, that also might lead to fresh immunity for our slimy friends.

And that’s where the researchers are taking their studies to next.

The paper, “Circulating Biomphalaria glabrata hemocyte subpopulations possess shared schistosome glycans and receptors capable of binding larval glycoconjugates,” was published in Experimental Parasitology by the University of Wisconsin’s Timothy Yoshino, Xiao-Jun Wu, and Laura Gonzalez, and the Leiden University Medical Center’s Cornelis Hokke.

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About bigkingken

A science writer dedicated to proving that the Big Ten - or the Committee on Institutional Cooperation, if you will - is more than athletics.
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