25 November 2020
Monitoring immune molecules in mycetoma
Published online 15 July 2019
Key immune system molecules are detected in mycetoma, a chronic, destructive inflammatory disease.
Two molecules that accumulate in the microenvironment of a mycetoma could play significant roles in the immune response that leads to the lesion.
Mycetoma is recognised by the World Health Organization as a neglected disease with serious long-term adverse health and economic effects. It can be caused by a wide variety of fungi or bacteria that penetrate the skin, leading to inflammation and a significant swelling. Inflammation is part of the natural immune response to infections, but it can also become harmful. It is important to learn more about the immune system molecules involved in mycetoma due to the central role of inflammation in this disease.
Researchers in Sudan and the Netherlands studied the levels of two key proteins of the immune system — interleukin-17 (IL-17) and matrix metalloprotein-9 (MMP-9) — in biopsy samples from 100 mycetoma patients.
Emmanuel Siddig of the Mycetoma Research Centre at the University of Khartoum, Sudan explains that previous studies have not investigated these proteins in relation to the disease.
IL-17 is an inflammatory signalling protein released by T-cells of the immune system. It is involved in the damaging inflammation found in a variety of chronic diseases. MMP-9 is an enzyme that breaks down the material surrounding cells, known as the extracellular matrix. It plays a role in the progression of some diseases, including rheumatoid arthritis, cancers, and cardiovascular conditions.
The microbes that cause mycetoma accumulate in structures called grains. The researchers detected IL-17 and MMP-9 production by cells surrounding these grains, and found evidence of increasing amounts of IL-17 as the mycetomas grew and aged.
The researchers detected differences in IL-17 and MMP-9 levels in each of the three zones of inflammation that surround the grains. They also found that MMP-9 levels varied depending on the specific microbes causing different mycetomas.
The possible significance of the proteins was also explored in mouse experiments. This work revealed reduced grain formation in mice lacking IL-17, suggesting a significant role for the protein in the onset of the disease.
“This is a baseline study,” says Siddig. “It will guide us to better understand the role of the immune response [in the disease],” which, the researchers hope, could lead to new treatment options.
Siddig, E. E. et al. Interleukin-17 and matrix metalloprotease-9 expression in the mycetoma granuloma. PLOS Negl. Trop. Dis. 13(7), e0007351 (2019).