Curbing Candida: The cells that keep fungal infections at bay: Without cells that spur on the specialized antifungal units, the fight against a common infection is a lost cause

Of all the fungi that live in the human body, the most infamous is probably the yeast Candida. This distant cousin of baker’s yeast is notorious for causing various types of thrush that can be a major nuisance, but it can also lead to an invasive infection that may, on occasion, prove fatal. In a study published today in Nature Immunology, a Weizmann Institute of Science research team headed by Prof. Jakub Abramson uncovered a previously unknown defense mechanism employed by the immune system in fighting Candida infections.

Candida is present at low levels in the bodies of most healthy people, forming part of the microbiome — a diverse spectrum of microbes that reside peacefully in our gut and on our skin. Under normal circumstances, Candida is held in check by the immune system, but it can occasionally grow excessively, invading the lining of the mouth, the vagina, the skin or other parts of the body. In severe cases, it can spread to the bloodstream and from there to the kidneys. Such life-threating infections may occur when a person’s immune system has been weakened, for example, by AIDS or by immunosuppressive drugs such as cancer chemotherapy or steroids. Antibiotics, which wipe out many of the beneficial bacteria within our microbiome, can also unleash local or invasive Candida eruptions by providing this yeast with an unfair advantage vis-à-vis other microorganisms. That’s why, for instance, women sometimes develop a vaginal yeast infection after taking antibiotics.

Until now, the immune cells that got most of the credit for defending the body against Candida were the small, round lymphocytes of the T cell type, called TH17. These cells were also the ones to take the blame when this defense failed.

In the new study, postdoctoral fellow Dr. Jan Dobeš, working together with colleagues in Abramson’s lab in Weizmann’s Immunology and Regenerative Biology Department, discovered that a powerful commando unit of TH17 cells capable of fighting Candida cannot be generated without crucial early support from an entirely different contingent: a subset of rare lymphoid cells known as type-3 innate lymphoid cells, or ILC3, that express a gene called the autoimmune regulator, or Aire

The two groups of cells belong to the two different arms of the immune system, which, like foot patrols and specialized units, join forces against a common enemy. The Aire-ILC3s — part of the more ancient, innate arm — spring into action almost immediately upon encountering a threat — in this case, a Candida infection. The TH17s belong to the immune system’s more recent, adaptive arm, which takes several days or even weeks to respond, but which launches a much more targeted and potent attack than the innate one.

The scientists found that as soon as Candida starts infecting tissues, the Aire-ILC3s engulf the yeast whole, chop them up and display some of the yeast pieces on their surfaces. That’s how these bits are presented to the TH17s, a few of which are generally on call in the lymph nodes, ready for an infection alert. This kind of presentation instructs the specialized T cells to start dividing rapidly, soaring in number from a few lone commandos to several hundred or even thousands of Candida-specific fighters, capable of destroying the yeast at the sites of infection.

Source: Read Full Article