Summary: A subset of taste cells may play a key role in the body’s immune response to harmful oral microbes. The findings could help taste loss associated with infections, aging, and dysregulation of the oral microbiome caused by chemotherapy.
Source: University of Nebraska Lincoln
Taste cells are heavily exposed to the microbes in the mouth, but their role in helping the body respond to those microbes has not yet been studied in detail.
A recent study from a team of researchers from the University of Nebraska–Lincoln and other institutions, however, has found that a subset of taste cells called type II taste cells may play a key role in the body’s immune response to harmful oral microbes.
The results of the three-year study, which was recently published in PLOS Biology, could help treat taste loss when conditions such as infection, aging, obesity and cancer chemotherapy cause dysregulation of the oral microbiome.
Microfold cells, which are specialized epithelial cells in the gut and tonsils, take samples of microbiota and pass them on to immune cells in the respective tissue through a process called transcytosis. This allows those immune cells to orchestrate an appropriate immune response.
The researchers found that Spib, a key gene required for the development of M cells, is also expressed in type II taste cells and wanted to determine whether the taste cells have the same immune-related function as the M cells.
“This study breaks new ground by demonstrating that type II taste cells function like M cells in responding to the microbiota,” said Sunil Sukumaran, assistant professor of nutrition and health and the corresponding author of the study.
“M cells are key to maintaining a healthy microbiota in the gut, and our finding suggests that type II taste cells do the same, in addition to their known roles in taste signaling.”
Using mouse models, the researchers determined that RANKL, a growth factor required for the development of M cells in the gut and tonsils that works through the Spib gene, can also promote M cell growth in taste tissue.
Spib knockout mice also showed dysregulation of immune signaling pathways in taste papillae and had much lower numbers of immune cells in the taste papillae. Curiously, they also had stronger attraction to sweet and umami tastants.
“Until recently, our understanding of how taste cells respond to microbes in the oral cavity was very limited,” Sukumaran said.
“The widespread loss of taste in COVID-19 patients highlighted this understudied area of taste research. We believe that discovering the M cell pathway in taste cells is a big step toward preventing and treating infection-associated taste loss.”
Type II taste cells participate in mucosal immune surveillance
The oral microbiome is second only to its intestinal counterpart in diversity and abundance, but its effects on taste cells remains largely unexplored.
Using single-cell RNASeq, we found that mouse taste cells, in particular, sweet and umami receptor cells that express taste 1 receptor member 3 (Tas1r3), have a gene expression signature reminiscent of Microfold (M) cells, a central player in immune surveillance in the mucosa-associated lymphoid tissue (MALT) such as those in the Peyer’s patch and tonsils.
Administration of tumor necrosis factor ligand superfamily member 11 (TNFSF11; also known as RANKL), a growth factor required for differentiation of M cells, dramatically increased M cell proliferation and marker gene expression in the taste papillae and in cultured taste organoids from wild-type (WT) mice.
Taste papillae and organoids from knockout mice lacking Spib (SpibKO), a RANKL-regulated transcription factor required for M cell development and regeneration on the other hand, failed to respond to RANKL. Taste papillae from SpibKO mice also showed reduced expression of NF-κB signaling pathway components and proinflammatory cytokines and attracted fewer immune cells.
However, lipopolysaccharide-induced expression of cytokines was strongly up-regulated in SpibKO mice compared to their WT counterparts. Like M cells, taste cells from WT but not SpibKO mice readily took up fluorescently labeled microbeads, a proxy for microbial transcytosis.
The proportion of taste cell subtypes are unaltered in SpibKO mice; however, they displayed increased attraction to sweet and umami taste stimuli. We propose that taste cells are involved in immune surveillance and may tune their taste responses to microbial signaling and infection.