Platelets have always been known for their function in helping blood cells clot. But the cells may also play a crucial role in identifying and shuttling dangerous bacteria to immune cells, according to a study published today (October 30) in Nature Immunology. The findings could one day help researchers develop new ways to mobilize the immune system for vaccines or therapies.
“All the bacteria that we looked at are associated with a platelet,” said Dirk Busch, lead author on the study and a medical microbiologist and immunologist at the Institute for Medical Microbiology, Immunology and Hygiene in Germany. “This was a big, big surprise, because nobody has described this before.” The team also found the specific protein on the platelets that seemed to interact with the bacteria.
“It’s interesting,” agreed immunologist Peter Lachmann of Cambridge University, who was not involved in the study. “The idea that platelets carry Listeria to dendritic cells, I think, is somewhat original.”
For years, Busch and his colleagues have known that the bacterium Listeria monocytogenes, which causes flu-like symptoms, was rapidly ferried from the blood to CD8a+ immune cells in the spleen, which play a critical role in launching T-cell production against bacteria that are hiding within cells. That raised the question of how the bacteria were getting to the spleen.
In the new study, they found that the Listeria that made it to the spleen were coated in a soluble factor called complement, the immune system’s rapid, all-purpose defense against a wide range of infections. When they created mice that were deficient in complement, the bacteria did not induce the T-cell response via the CD8a+ cells, suggesting that complement was somehow involved in the process. But that raised yet another question—how was the bacteria becoming coated with complement?
To find out, the researchers labeled Listeria cells with fluorescent tags and watched as they migrated through the bloodstream. To their surprise, they found that the bacterial cells were being chaperoned by blood platelets.
The team tested also looked at other species of bacteria, and saw that platelets played a similar role for many gram positive infections. The results suggest that the platelets are critical for flagging bacteria with complement, which then serves to jumpstart a targeted immune response. The researchers also documented an increase in a platelets in the spleen, suggesting the cells also play a role in shuttling the bacteria to the CD8a+ cells, Busch said.
While exciting, the results are so far limited to a single mouse model, Lachmann warned. “You must be very careful to extending this from mice to other species," he said, because they have a complement receptor not found in other species." The mouse is distinctly odd in regard to complement clearance mechanism.” In addition, the spleen plays a much more prominent role in the immune system in mice, as compared to humans, he added.
But if the same mechanism holds true for humans, “Since CD8a+ dendritic cells are believed to play an important role in the induction of immunity,” specifically targeting a vaccine to these cells one day be used to boost vaccine or therapy effectiveness, Busch said.