Creative Minds: Does Human Immunity Change with the Seasons?

Micaela Martinez

Micaela Martinez

It’s an inescapable conclusion from the book of Ecclesiastes that’s become part of popular culture thanks to folk legends Pete Seeger and The Byrds: “To everything (turn, turn, turn), there is a season.” That’s certainly true of viral outbreaks, from the flu-causing influenza virus peaking each year in the winter to polio outbreaks often rising in the summer. What fascinates Micaela Martinez is, while those seasonal patterns of infection have been recognized for decades, nobody really knows why they occur.

Martinez, an infectious disease ecologist at Princeton University, Princeton, NJ, thinks colder weather conditions and the tendency for humans to stay together indoors in winter surely play a role. But she also thinks an important part of the answer might be found in a place most hadn’t thought to look: seasonal changes in the human immune system. Martinez recently received an NIH Director’s 2016 Early Independence Award to explore fluctuations in the body’s biological rhythms over the course of the year and their potential influence on our health.

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Rare Disease Mystery: Nodding Syndrome May Be Linked to Parasitic Worm

Rural Uganda village gathering

Caption: Village in the East Africa nation of Uganda
Credit: Centers for Disease Control and Prevention

In the early 1960s, reports began to surface that some children living in remote villages in East Africa were suffering mysterious episodes of “head nodding.” The condition, now named nodding syndrome, is recognized as a rare and devastating form of epilepsy. There were hints that the syndrome might be caused by a parasitic worm called Onchocerca volvulus, which is transmitted through the bites of blackflies. But no one had been able to tie the parasitic infection directly to the nodding heads.

Now, NIH researchers and their international colleagues think they’ve found the missing link. The human immune system turns out to be a central player. After analyzing blood and cerebrospinal fluid of kids with nodding syndrome, they detected a particular antibody at unusually high levels [1]. Further studies suggest the immune system ramps up production of that antibody to fight off the parasite. The trouble is those antibodies also react against a protein in healthy brain tissue, apparently leading to progressive cognitive dysfunction, neurological deterioration, head nodding, and potentially life-threatening seizures.

The findings, published in Science Translational Medicine, have important implications for the treatment and prevention of not only nodding syndrome, but perhaps other autoimmune-related forms of epilepsy. As people in the United States and around the globe today observe the 10th anniversary of international Rare Disease Day, this work provides yet another example of how rare disease research can shed light on more common diseases and fundamental aspects of human biology.

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Find and Replace: DNA Editing Tool Shows Gene Therapy Promise

Neutrophil being edited with CRISPR/Cas9

Caption: This image represents an infection-fighting cell called a neutrophil. In this artist’s rendering,  the cell’s DNA is being “edited” to help restore its ability to fight bacterial invaders.
Credit: NIAID, NIH

For gene therapy research, the perennial challenge has been devising a reliable way to insert safely a working copy of a gene into relevant cells that can take over for a faulty one. But with the recent discovery of powerful gene editing tools, the landscape of opportunity is starting to change. Instead of threading the needle through the cell membrane with a bulky gene, researchers are starting to design ways to apply these tools in the nucleus—to edit out the disease-causing error in a gene and allow it to work correctly.

While the research is just getting under way, progress is already being made for a rare inherited immunodeficiency called chronic granulomatous disease (CGD). As published recently in Science Translational Medicine, a team of NIH researchers has shown with the help of the latest CRISPR/Cas9 gene-editing tools, they can correct a mutation in human blood-forming adult stem cells that triggers a common form of CGD. What’s more, they can do it without introducing any new and potentially disease-causing errors to the surrounding DNA sequence [1].

When those edited human cells were transplanted into mice, the cells correctly took up residence in the bone marrow and began producing fully functional white blood cells. The corrected cells persisted in the animal’s bone marrow and bloodstream for up to five months, providing proof of principle that this lifelong genetic condition and others like it could one day be cured without the risks and limitations of our current treatments.

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Snapshots of Life: Virus Hunting with Carbon Nanotubes

H5N2 trapped in carbon nanotubes

Credit: Penn State University

The purple pods that you see in this scanning electron micrograph are the H5N2 avian flu virus, a costly threat to the poultry and egg industry and, in very rare instances, a health risk for humans. However, these particular pods are unlikely to infect anything because they are trapped in a gray mesh of carbon nanotubes. Made by linking carbon atoms into a cylindrical pattern, such nanotubes are about 10,000 times smaller than width of a human hair.

The nanotubes above have been carefully aligned on a special type of silicon chip called a carbon-nanotube size-tunable-enrichment-microdevice (CNT-STEM). As described recently in Science Advances, this ultrasensitive device is designed to capture viruses rapidly based on their size, not their molecular characteristics [1]. This unique feature enables researchers to detect completely unknown viruses, even when they are present in extremely low numbers. In proof-of-principle studies, CNT-STEM made it possible to collect and detect viruses in a sample at concentrations 100 times lower than with other methods, suggesting the device and its new approach will be helpful in the ongoing hunt for new and emerging viruses, including those that infect people.

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Could Zika Virus Have Lasting Impact on Male Fertility?

zika-histology

Caption: Immunofluorescence staining showing that the testes of Zika-free mice (left) are full of developing sperm (pink), while the testes of Zika-infected mice (right) contain very few sperm.
Credit: Prabagaran Esakky, Washington University School of Medicine, St. Louis

Recent research has shown that the mosquito-borne Zika virus has the potential to cause serious health problems, including severe birth defects in humans. But the damaging effects of Zika might not end there: results of a new mouse study show that the virus may also have an unexpected negative—and possibly long-lasting—impact on male fertility.

In work published in the journal Nature, an NIH-funded research team found that Zika infections can persist for many weeks in the reproductive systems of male mice [1]. As a result of this infection, levels of testosterone and other sex hormones drop, sperm counts fall, and, in some animals, the testicles shrink to 1/10th of their normal size, possibly irreversibly. All of this adds up to Zika-infected male mice that are significantly less fertile than their healthy counterparts—producing about a quarter as many viable offspring as normal when mated with female mice. While mice are certainly not humans, the results underscore the urgent need for additional research to examine the full spectrum of Zika’s health effects in men, women, and children of both sexes.

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