New Imaging Approach Reveals Lymph System in Brain

Considering all the recent advances in mapping the complex circuitry of the human brain, you’d think we’d know all there is to know about the brain’s basic anatomy. That’s what makes the finding that I’m about to share with you so remarkable. Contrary to what I learned in medical school, the body’s lymphatic system extends to the brain—a discovery that could revolutionize our understanding of many brain disorders, from Alzheimer’s disease to multiple sclerosis (MS).

Researchers from the National Institute of Neurological Disorders and Stroke (NINDS), the National Cancer Institute (NCI), and the University of Virginia, Charlottesville made this discovery by using a special MRI technique to scan the brains of healthy human volunteers [1]. As you see in this 3D video created from scans of a 47-year-old woman, the brain—just like the neck, chest, limbs, and other parts of the body—possesses a network of lymphatic vessels (green) that serves as a highway to circulate key immune cells and return metabolic waste products to the bloodstream.

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Ebola Virus: Lessons from a Unique Survivor

Ebola virus

Caption: Ebola virus (green) is shown on cell surface.
Credit: National Institutes of Allergy and Infectious Diseases, NIH

There are new reports of an outbreak of Ebola virus disease in the Democratic Republic of Congo. This news comes just two years after international control efforts eventually contained an Ebola outbreak in West Africa, though before control was achieved, more than 11,000 people died—the largest known Ebola outbreak in human history [1]. While considerable progress continues to be made in understanding the infection and preparing for new outbreaks, many questions remain about why some people die from Ebola and others survive.

Now, some answers are beginning to emerge thanks to a new detailed analysis of the immune responses of a unique Ebola survivor, a 34-year-old American health-care worker who was critically ill and cared for at the NIH Special Clinical Studies Unit in 2015 [2]. The NIH-led team used the patient’s blood samples, which were drawn every day, to measure the number of viral particles and monitor how his immune system reacted over the course of his Ebola infection, from early symptoms through multiple organ failures and, ultimately, his recovery.

The researchers identified unexpectedly large shifts in immune responses that preceded observable improvements in the patient’s symptoms. The researchers say that, through further study and close monitoring of such shifts, health care workers may be able to develop more effective ways to care for Ebola patients.

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Snapshots of Life: Fighting Urinary Tract Infections

Urinary tract infection in a mouse

Source: Valerie O’Brien, Matthew Joens, Scott J. Hultgren, James A.J. Fitzpatrick, Washington University, St. Louis

For patients who’ve succeeded in knocking out a bad urinary tract infection (UTI) with antibiotic treatment, it’s frustrating to have that uncomfortable burning sensation flare back up. Researchers are hopeful that this striking work of science and art can help them better understand why severe UTIs leave people at greater risk of subsequent infection, as well as find ways to stop the vicious cycle.

Here you see the bladder (blue) of a laboratory mouse that was re-infected 24 hours earlier with the bacterium Escherichia coli (pink), a common cause of UTIs. White blood cells (yellow) reach out with what appear to be stringy extracellular traps to immobilize and kill the bacteria.

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Creative Minds: Interrogating a Master of Disguise

Monica Mugnier

Monica Mugnier

When I volunteered several years ago as a physician in a small hospital in West Africa, one of the most frustrating and frightening diseases I saw was sleeping sickness. Now, an investigator supported by the NIH Common Fund aims to figure out how this disease pathogen manages to evade the human immune system.

Monica Mugnier’s fascination with parasites started in college when she picked up the book Parasite Rex, a riveting, firsthand account of how “sneaky” parasites can be. The next year, while studying abroad in England, Mugnier met a researcher who had studied one of the most devious of parasites—a protozoan, spread by blood-sucking tsetse flies, that causes sleeping sickness in humans and livestock across sub-Saharan Africa.

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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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