A new study "Oral epithelial cells orchestrate innate type 17 responses to Candida albicans through the virulence factor candidalysin," which is published in Science Immunology last week, sheds light on how the immune system reacts to the opportunistic pathological fungi in the mouth.
Oral microbiology investigates the microbes in the mouth and their interactions with the host body. The environment in the human mouth allows the growth of a variety of oral microbes, especially bacteria and fungi. Under normal conditions, these oral microbes do not cause illness. However, when the immune system is weakened, diseases occur.
Candida albicans is a normal fungus found in the human mouth. This type of fungus also presents in the respiratory, gastrointestinal, and female genital tracts. C. albicans is a prevalent cause of fungal infection around the world. When the fungus accumulates on the lining of the mouth, it triggers an illness called oral thrush, which is characterized by white lesions on the tongue or inner cheeks. Oral thrush is occasionally accompanied by pain and fever. Babies and individuals infected with HIV are more likely to develop oral thrush due to a weaker immune system.
Although fungal infections are very common, human immunity against fungi in the mouth remains largely unknown. And so far, no anti-fungal vaccines have been created. One thing that makes fungi so hard to fight is that they can exist in multiple forms according to the environment. For example, C. albicans can switch from a usual unicellular yeast-like form to an invasive, multicellular filamentous form. In response to environmental changes, C. albicans will convert into its invasive form that produces long, filamentous hyphae. The hyphae can penetrate the oral epithelial cells (OECs), the cells that line the mouth cavity.
A team, led by Dr. Sarah Gaffen from the University of Pittsburgh in the USA and Dr. Julian Naglik from King's College London in the UK, set out to explore why C. albicans rarely affects healthy individuals. In the former research, Dr. Gaffen and colleagues discovered that the cytokine IL-17
and the immune cells that produce it are required for immunity against C. albicans. The OECs provide the first line of defense against pathogens in the mouth. When C. albicans begins to grow hyphae, the OECs promotes the production of IL-17 by the immune cells.
For the current study, the team carried out a series of experiments to demonstrate that it is a toxin secreted by C. albicans that helps the fungus to invade OECs. The toxin, known as candidalysin, is a hypha-associated protein and virulence factor. C. albicans that lacked candidalysin caused less epithelial damage. Additionally, the team found that IL-17 and candidalysin work together to potentiate the anti-fungal responses. Collectively, the results indicate that anti-fungal immunity is induced by candidalysin-associated cellular damage and is further amplified by IL-17-mediated inflammation.
The study may not only accelerate the development of new vaccines and therapeutics for C. albicans, but also have implications for research on other fungi.