Researchers have shown that how the innate immune system, which responds more generally to dangers detected in the body, can be trained to remember past threats and respond more robustly to future challenges. The study results were in The Journal of Cell.
The scientists showed that this innate immune training, mediated by the compound β-glucan, derived from the fungus, takes place at the level of the bone marrow. The findings point to a strategy by which one could prime the immune system prior to entering a situation where the risk of contracting an infection was high, or prior to receiving chemotherapy to avoid neutropenia, a depletion of the immune system's neutrophils.
Taking β-glucan prior to chemotherapy would be a very good application. In the case of infections, β-glucan would activate your innate immune system so it would be poised to respond much faster and stronger to an infection. However, the dogma in immunology was that the adaptive immune system possesses a memory, which is why vaccines are effective even years later, while the innate immune system does not.
However, the study showed that the innate immune system can be trained to have a robust response by challenging it with various stimuli, such as β-glucan, a sugar molecule found in fungus. These initial investigations of innate immune training suggested that this effect was mediated by epigenetic changes to mature myeloid cells: neutrophils, monocytes, macrophages and others.
While, the team assumed that the changes had to somehow affect the bone marrow, the site of hematopoietic stem cells, and specifically those that serve as myeloid cell precursors. To test this prediction, they gave mice a single injection of β-glucan and found that within a day their HSCs expanded in number. There was a bias toward myelopoesis, the generation of myeloid precursor cells.
When they transplanted HSCs from mice that received either β-glucan or a control injection four weeks earlier into mice lacking HSCs, they found that the mice that received cells from the β-glucan group produced more cells of myeloid lineage. To see if this myeloid cell expansion had a protective effect, the researchers challenged mice that had received β-glucan or a control with a substance that mimics a bacterial infection.
They found that the β-glucan mice had a greater production of myeloid cells and less evidence of DNA damage in their HSCs compared to the control group. The β-glucan challenge also had a beneficial impact after chemotherapy. While chemotherapeutics can deplete critical immune cells, the researchers found β-glucan stimulation resulted in mice having white blood cells after treatment with two common chemotherapeutic drugs.
The team said the mice treated with β-glucan were healthy to start and their immune systems were invigorated. However, what would happen if the mice already had a chronic condition or were older was not clear. The immune systems could be poised to overrespond to perceived dangers and worsen a chronic inflammatory disease. The researchers would follow up the work along several avenues, including looking at innate immune system training in the context of ageing and seeing how it affects the course of a variety of disease conditions, including the gum disease periodonditis.