By Emma Yasinski
Dentists and doctors may be able to “train” their patients’ innate immune cells to protect against infections in the mouth, at a time when the risk of infection is high, such as during chemotherapy, according to a recent study in Cell.
“This innate immune training takes place in the bone marrow and results in the production of increased numbers of white blood cells (neutrophils) that can readily fight infections in the oral cavity and elsewhere in the body,” lead author, George Hajishengallis, DDS, PhD, told Incisor in an email interview.
“This could be a strategy to prime the immune system not only prior to a situation where the risk of infection is high, but also prior to chemotherapy to prevent depletion of our immune system's neutrophils,” explained Dr. Hajishengallis, who is a professor at the University of Pennsylvania School of Dental Medicine.
One troubling side effect of chemotherapy is an increased risk of infection in the mouth. Chemotherapy kills cancer cells, but also the cells that patients need to protect themselves against opportunistic infections. These infections can cause pain, difficulty eating, damage to teeth, and in some cases, may be severe enough for a doctor to delay or end a patient’s chemotherapy.
How Could This Be Possible?
Most people are familiar with adaptive immunity, the type of immunity triggered by vaccines. The immune system develops specific cells that recognize specific pathogens the body has seen before, so that it can fight off the infection more readily a second time. But innate immunity has long been thought to be non-specific, and incapable of adapting in response to invaders.
That changed in 2016, when a group published a paper challenging the tenet, suggesting that innate immunity could, in fact, be trained to have a heightened response for months after exposure to invaders or vaccines. Still, many scientists wondered how this could be possible. The cells in the innate immune system- myeloid cells- live relatively short lives. So, the dogma suggested, they couldn’t possibly “remember” previous invaders.
Dr. Hajishengallis and his team had an idea. The individual myeloid cells don’t live very long, but they’re constantly being produced in the bone marrow. Maybe there were changes in the bone marrow, which houses the hematopoietic stem cells (HSCs) - stem cells that give rise to myeloid cells - that allowed new cells to “remember” threats the body had previously encountered.
They tested this theory by giving mice injections of β-glucan, a compound derived from a fungus. The next day, they examined the numbers of hematopoietic stem cells in each mouse, and specifically, how many gave rise to myeloid cells (HSCs can produce more than one type of cell.)
The mice that received the β-glucan injection not only had more HSCs but also, more myeloid precursor cells than their counterparts who received a control injection.
“We showed that the effects of trained immunity are mediated through modulation of hematopoietic progenitors in the bone marrow, thus can give rise to many generations of mature cells with improved features,” said Dr. Hajishengallis.
More Work Ahead
Next, the team went on to show that the effects outlasted the lives of the individual cells. They transplanted HSCs from mice that had received the β-glucan injections or control injections into mice that didn’t have HSCs. The mice who received the cells from the rodents that had the β-glucan injection produced more myeloid cells than the those that were transplanted with cells from the mice that had received control injections.
Lastly, and most importantly, Dr. Hajishengallis and his colleagues showed that this increase in myeloid cells had a protective effect against both a simulated bacterial infection and the immune-depleting effects of chemotherapy.
In response to the simulated bacterial infection, mice that had been previously injected with β-glucan, not only had more myeloid cells but also experienced less DNA damage than their counterparts. The researchers also tested two common chemotherapeutic drugs on the mice and showed that those rodents that had been exposed to β-glucan were able to produce more white blood cells after the chemotherapy, protecting them from some opportunistic infections, and allowing them to live longer than the mice that did not receive the injection.
Dr. Hajishengallis emphasized that this discovery could be very valuable to dentists with patients undergoing chemotherapy, but that there is a lot more work ahead. One of the future directions of the research is to examine more specifically how the immune training might be used in cases of periodontitis.
Additionally, a heightened immune response can be dangerous in certain situations. “One needs to be cautious about innate immune training,” Dr. Hajishengallis emphasized. “A heightened state of innate immunity might lead to enhanced inflammatory responses that can potentially lead to tissue damage in the setting of chronic inflammatory diseases.”