Poor Influenza Infection Leads to Surprising Discovery of "Taste Bud Cells"

Most people who are resistant to influenza infection recover completely after a week or two. But for some, a severe case of influenza can actually reshape the architecture of their lungs and forever compromise their respiratory function.

With a surprising new discovery, Penn researchers identified what they saw as a major feature of this remodeling process. When the team examined the lungs of mice after a severe flu, she found cells virtually identical to those found in the taste buds. Scientists discovered the origin of these "taste bud cells," also known as solitary chemosensory cells or tufted cells, and came from the same cell line as those known to cause damaging lung remodeling. After further studies, this discovery could provide insight into the possibilities of protecting lung function in people with serious influenza infections.

"It was really very strange to see, because those cells are not in the lungs at first," says Andrew E. Vaughan, lead author and team leader, a biologist at Penn's School of Veterinary Medicine. "As close as possible is normally in the trachea. What we did was show where they came from and how that same kind of rare cell that gives you all that sickly lung remodeling after the flu is also causing these ectopic tufted cells. "

The research was published this week in the American Journal of Physiology – Cellular and Molecular Pulmonary Physiology.

Interested in how the lungs can regenerate after an injury, Vaughan and his colleagues have for years been paying special attention to how the lungs respond to the flu. In 2015, they published an article in Nature identifying a new clbad of cells, epithelial progenitors of negative lineage, such as those giving way to the tissue structure of the remodeled lung following severe pulmonary infections. But they also noticed that this restructuring was accompanied by persistent inflammation, even long after the elimination of the flu virus. Curious to explore the link between lung remodeling and lingering inflammation, Vaughan speaks to Penn's School of Medicine otolaryngologist Noam A. Cohen and Penn's immunologist De'Broski R. Herbert. Vet.

Together, they took a closer look at what was happening after the exposure of mice to a virulent infection with the H1N1 virus. While an acute influenza infection evokes what is called a type 1 immune response in the body, the researchers found that cell types and signaling markers that were elevated several weeks after animal infections were characteristic of the type 2 immune response, one more badociated with allergies, asthma, nasal polyps and even hookworm infections.

"These distinctive signs of a type 2 immune response after influenza were unexpected and have remained largely unnoticed until very recently," says Vaughan.

According to other studies on type 2 immunity in the mouse intestine, researchers knew that clumped cells were needed to orchestrate this type of response. The researchers went to get them in the lungs. "And there they were everywhere," says Vaughan.

"We had examined these solitary chemosensory cells in patients with nasal polyps and found a mbadive increase in the nose of these patients," says Cohen. "Interestingly, one of the hallmarks of these cells is also found in the lungs of asthmatics. Nasal polyps are found in about 50% of asthmatic patients. These recent findings may be a link between type 2 inflammatory diseases, such as asthma, and nasal polyps, following a viral respiratory infection. "

The researchers noted that these clumps of cells covered the airways and alveoli of the lungs, which are the same places as cells responsible for post-influenza structural changes. By affixing a fluorescent marker on the negative lineage epithelial progenitor cells, they discovered that it was precursors of the cells of the bunch and cells responsible for long-term deficits in function and structure lungs.

To understand what solitary "bud-bud" cells did in the lungs after influenza, the researchers tried to activate them using bitter compounds. This stimulation not only caused an increase in the number of cells in the bunch, but also triggered acute inflammation. In uninfected and therefore tufous-free lungs, no such inflammation has occurred.

Penn's team is eager to continue this path of research. "In mice, we would like to go further and see how the presence of these cells affects the quality of regeneration after an infection," Vaughan says. If one can exploit their activity, he notes, there may be a way to avoid the long-term detrimental remodeling that occurs after an infection.

They will also look at human lung samples to confirm that the same phenomenon observed in mice also occurs in people with severe respiratory infections. Vaughan says that there is some clue that this might be the case, as evidence from histology. The presence of clumps of cells and their involvement in allergies and asthma could also help explain why young children who contract serious viral infections, such as the respiratory syncytial virus, are predisposed to the development of lymphatic infections. asthma later in life.

And as it has been proven that the presence of clump cells in the intestines confers immunity to certain diseases, such as hookworm, researchers want to know if this is the case of clump cells in the lungs.

This article has been republished from documents provided by the University of Pennsylvania. Note: Content may have changed for length and content. For more information, please contact the cited source.

Reference
Development of solitary chemosensory cells in the distal lung after severe influenza injury. Chetan K Rane et al. American Journal of Pulmonary Physiology – Cellular and Molecular Physiology, https://doi.org/10.1152/ajplung.00032.2019.