Deadly fungal infections affect millions of people around the world. These fungal infections often originate in the patient’s gut, before migrating to the bloodstream and overwhelming the rest of the body, particularly for immunocompromised patients. Especially as drug-resistant fungal strains develop, the need for preventative treatments is growing. Many viral and bacterial infections can be prevented by administering vaccines which trigger an immune system response, spurring the creation of specific antibodies that are capable of neutralizing the virus or bacteria in question. In contrast, a wide spread of deadly fungal infections currently have no such options. However, recent studies of gut fungal populations show potential links between the fungal species found in a human’s gut and the human’s antifungal antibodies, which boost the human’s immune system protection against certain fungal infections.

In order to explore the relationship between the specific profile of gut fungi and the profile of the host’s antifungal antibodies, Itai Doron and collaborators developed a mouse study. The guts of healthy mice were populated with fungi from the Candida genus, which is the most common cause of fungal infections. The presence of this fungus led to a production of antifungal antibodies in the bloodstreams of the mice. The mice did not develop full-blown fungal infections, but their immune systems were exposed to enough of the fungi to learn how fight back. The next step was to populate the guts of immunocompromised mice with this fungus population. The fungi spread to the bloodstream of the already-weakened mice, leading to deadly infections. However, the immunocompromised mice could be saved by being treated with purified antibodies taken from the healthy mice. These antibodies were enough to boost the immune system of the previously immunocompromised mice, thus protecting them from infection. 

Humans with a decreased amount of antifungal antibodies are more susceptible to dangerous fungal infections. The work here shows a promising path for developing a fungus vaccine by populating the gut of healthy people with the fungal population for which immunity is desired. Perhaps even more exciting is that this work shows a first possibility of developing an antifungal antibody therapy to protect immunocompromised patients from these dangerous fungal infections.

Itai Doron is a graduate student at Weill Cornell Medicine, in the group of Professor Iliyan Iliev, who is an Associate Professor of Microbiology and Immunology. This work was done with collaborators at Weill Cornell Medicine, as well as collaborators from the Laboratory of Human Genetics of Infectious Diseases in Paris.

Managing Correspondent: Anne Hébert

Original article: Human gut mycobiota tune immunity via CARD9-dependent induction of anti-fungal IgG antibodies – Cell

Media coverage: Fungi in the gut prime immunity against infection – Weill Cornell Medicine

Image credit: Candida Pap (from Wikimedia)

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