Posted on by Dr. Francis Collins
Most people who get the flu bounce right back in a week or two. But, for others, the respiratory infection is the beginning of lasting asthma-like symptoms. Though I had a flu shot, I had a pretty bad respiratory illness last fall, and since that time I’ve had exercise-induced asthma that has occasionally required an inhaler for treatment. What’s going on? An NIH-funded team now has evidence from mouse studies that such long-term consequences stem in part from a surprising source: previously unknown lung cells closely resembling those found in taste buds.
The image above shows the lungs of a mouse after a severe case of H1N1 influenza infection, a common type of seasonal flu. Notice the oddball cells (green) known as solitary chemosensory cells (SCCs). Those little-known cells display the very same chemical-sensing surface proteins found on the tongue, where they allow us to sense bitterness. What makes these images so interesting is, prior to infection, the healthy mouse lungs had no SCCs.
SCCs, sometimes called “tuft cells” or “brush cells” or “type II taste receptor cells”, were first described in the 1920s when a scientist noticed unusual looking cells in the intestinal lining  Over the years, such cells turned up in the epithelial linings of many parts of the body, including the pancreas, gallbladder, and nasal passages. Only much more recently did scientists realize that those cells were all essentially the same cell type. Owing to their sensory abilities, these epithelial cells act as a kind of lookout for signs of infection or injury.
This latest work on SCCs, published recently in the American Journal of Physiology–Lung Cellular and Molecular Physiology, adds to this understanding. It comes from a research team led by Andrew Vaughan, University of Pennsylvania School of Veterinary Medicine, Philadelphia .
As a post-doc, Vaughan and colleagues had discovered a new class of cells, called lineage-negative epithelial progenitors, that are involved in abnormal remodeling and regrowth of lung tissue after a serious respiratory infection . Upon closer inspection, they noticed that the remodeling of lung tissue post-infection often was accompanied by sustained inflammation. What they didn’t know was why.
The team, including Noam Cohen of Penn’s Perelman School of Medicine and De’Broski Herbert, also of Penn Vet, noticed signs of an inflammatory immune response several weeks after an influenza infection. Such a response in other parts of the body is often associated with allergies and asthma. All were known to involve SCCs, and this begged the question: were SCCs also present in the lungs?
Further work showed not only were SCCs present in the lungs post-infection, they were interspersed across the tissue lining. When the researchers exposed the animals’ lungs to bitter compounds, the activated SCCs multiplied and triggered acute inflammation.
Vaughan’s team also found out something pretty cool. The SCCs arise from the very same lineage of epithelial progenitor cells that Vaughan had discovered as a post-doc. These progenitor cells produce cells involved in remodeling and repair of lung tissue after a serious lung infection.
Of course, mice aren’t people. The researchers now plan to look in human lung samples to confirm the presence of these cells following respiratory infections.
If confirmed, the new findings might help to explain why kids who acquire severe respiratory infections early in life are at greater risk of developing asthma. They suggest that treatments designed to control these SCCs might help to treat or perhaps even prevent lifelong respiratory problems. The hope is that ultimately it will help to keep more people breathing easier after a severe bout with the flu.
 Closing in on a century-old mystery, scientists are figuring out what the body’s ‘tuft cells’ do. Leslie M. Science. 2019 Mar 28.
 Development of solitary chemosensory cells in the distal lung after severe influenza injury. Rane CK, Jackson SR, Pastore CF, Zhao G, Weiner AI, Patel NN, Herbert DR, Cohen NA, Vaughan AE. Am J Physiol Lung Cell Mol Physiol. 2019 Mar 25.
 Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury. Vaughan AE, Brumwell AN, Xi Y, Gotts JE, Brownfield DG, Treutlein B, Tan K, Tan V, Liu FC, Looney MR, Matthay MA, Rock JR, Chapman HA. Nature. 2015 Jan 29;517(7536):621-625.
Asthma (National Heart, Lung, and Blood Institute/NIH)
Influenza (National Institute of Allergy and Infectious Diseases/NIH)
Vaughan Lab (University of Pennsylvania, Philadelphia)
Cohen Lab (University of Pennsylvania, Philadelphia)
Herbert Lab (University of Pennsylvania, Philadelphia)
NIH Support: National Heart, Lung, and Blood Institute; National Institute on Deafness and Other Communication Disorders
Posted on by Dr. Francis Collins
Researchers are making tremendous strides toward developing better ways to reduce our risk of getting the flu. And one of the latest ideas for foiling the flu—a “gene mist” that could be sprayed into the nose—comes from a most surprising source: llamas.
Like humans and many other creatures, these fuzzy South American relatives of the camel produce immune molecules, called antibodies, in their blood when exposed to viruses and other foreign substances. Researchers speculated that because the llama’s antibodies are so much smaller than human antibodies, they might be easier to use therapeutically in fending off a wide range of flu viruses. This idea is now being leveraged to design a new type of gene therapy that may someday provide humans with broader protection against the flu .
Posted on by Dr. Francis Collins
We live in a world energized by technological advances, from that new app on your smartphone to drones and self-driving cars. As you can see from this video, NIH-supported researchers are also major contributors, developing a wide range of amazing biomedical technologies that offer tremendous potential to improve our health.
Produced by the NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB), this video starts by showcasing some cool fluorescent markers that are custom-designed to light up specific cells in the body. This technology is already helping surgeons see and remove tumor cells with greater precision in people with head and neck cancer . Further down the road, it might also be used to light up nerves, which can be very difficult to see—and spare—during operations for cancer and other conditions.
Other great things to come include:
- A wearable tattoo that detects alcohol levels in perspiration and wirelessly transmits the information to a smartphone.
- Flexible coils that produce high quality images during magnetic resonance imaging (MRI) [2-3]. In the future, these individualized, screen-printed coils may improve the comfort and decrease the scan times of people undergoing MRI, especially infants and small children.
- A time-release capsule filled with a star-shaped polymer containing the anti-malarial drug ivermectin. The capsule slowly dissolves in the stomach over two weeks, with the goal of reducing the need for daily doses of ivermectin to prevent malaria infections in at-risk people .
- A new radiotracer to detect prostate cancer that has spread to other parts of the body. Early clinical trial results show the radiotracer, made up of carrier molecules bonded tightly to a radioactive atom, appears to be safe and effective .
- A new supercooling technique that promises to extend the time that organs donated for transplantation can remain viable outside the body [6-7]. For example, current technology can preserve donated livers outside the body for just 24 hours. In animal studies, this new technique quadruples that storage time to up to four days.
- A wearable skin patch with dissolvable microneedles capable of effectively delivering an influenza vaccine. This painless technology, which has produced promising early results in humans, may offer a simple, affordable alternative to needle-and-syringe immunization .
If you like what you see here, be sure to check out this previous NIH video that shows six more awesome biomedical technologies that your tax dollars are helping to create. So, let me extend a big thanks to you from those of us at NIH—and from all Americans who care about the future of their health—for your strong, continued support!
 Image-guided surgery in cancer: A strategy to reduce incidence of positive surgical margins. Wiley Interdiscip Rev Syst Biol Med. 2018 Feb 23.
 Screen-printed flexible MRI receive coils. Corea JR, Flynn AM, Lechêne B, Scott G, Reed GD, Shin PJ, Lustig M, Arias AC. Nat Commun. 2016 Mar 10;7:10839.
 Printed Receive Coils with High Acoustic Transparency for Magnetic Resonance Guided Focused Ultrasound. Corea J, Ye P, Seo D, Butts-Pauly K, Arias AC, Lustig M. Sci Rep. 2018 Feb 21;8(1):3392.
 Oral, ultra-long-lasting drug delivery: Application toward malaria elimination goals. Bellinger AM, Jafari M1, Grant TM, Zhang S, Slater HC, Wenger EA, Mo S, Lee YL, Mazdiyasni H, Kogan L, Barman R, Cleveland C, Booth L, Bensel T, Minahan D, Hurowitz HM, Tai T, Daily J, Nikolic B, Wood L, Eckhoff PA, Langer R, Traverso G. Sci Transl Med. 2016 Nov 16;8(365):365ra157.
 Clinical Translation of a Dual Integrin avb3– and Gastrin-Releasing Peptide Receptor–Targeting PET Radiotracer, 68Ga-BBN-RGD. Zhang J, Niu G, Lang L, Li F, Fan X, Yan X, Yao S, Yan W, Huo L, Chen L, Li Z, Zhu Z, Chen X. J Nucl Med. 2017 Feb;58(2):228-234.
 Supercooling enables long-term transplantation survival following 4 days of liver preservation. Berendsen TA, Bruinsma BG, Puts CF, Saeidi N, Usta OB, Uygun BE, Izamis ML, Toner M, Yarmush ML, Uygun K. Nat Med. 2014 Jul;20(7):790-793.
 The promise of organ and tissue preservation to transform medicine. Giwa S, Lewis JK, Alvarez L, Langer R, Roth AE, et a. Nat Biotechnol. 2017 Jun 7;35(6):530-542.
 The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): a randomised, partly blinded, placebo-controlled, phase 1 trial. Rouphael NG, Paine M, Mosley R, Henry S, McAllister DV, Kalluri H, Pewin W, Frew PM, Yu T, Thornburg NJ, Kabbani S, Lai L, Vassilieva EV, Skountzou I, Compans RW, Mulligan MJ, Prausnitz MR; TIV-MNP 2015 Study Group.
Center for Wearable Sensors (University of California, San Diego)
Hyperpolarized MRI Technology Resource Center (University of California, San Francisco)
Center for Engineering in Medicine (Massachusetts General Hospital, Boston)
Center for Drug Design, Development and Delivery (Georgia Tech University, Atlanta)
NIH Support: National Institute of Biomedical Imaging and Bioengineering; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases
Posted on by Dr. Francis Collins
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.
Posted on by Dr. Francis Collins
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 . 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.