Jahnavi Sarma
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Written By: Jahnavi Sarma | Published : February 6, 2021 1:03 PM IST
Normal intestinal fungi such as Candida albicans may function as a kind of intestinal vaccine against fungal infection in healthy people, by inducing the production of bloodborne antibodies that can target multiple species of potentially pathogenic fungi.
Infectious diseases can strike at any time and from anywhere. The COVID-19 pandemic has shown us the many dangers that may be lurking just around the corner. So how do you fight this danger? Experts have long told us that boosting our immunity is the best way to do this. There are many ways in which you can make your immune system strong and capable of fighting off invading pathogens. Now researchers from the Weill Cornell Medicine Graduate School of Medical Sciences say that common fungi, often present in the gut, can teach the immune system how to respond to their more dangerous relatives. Any breakdowns in this process can leave people susceptible to deadly fungal infections. The Cell published this study on Feb 5.
This new study, which looks at the complex relationship between humans and their associated microbes in a new manner, points the way toward new and better therapies that could help combat a rising tide of drug-resistant pathogens. The new discovery stemmed from earlier work on inflammatory bowel disease, a condition that often causes patients to carry larger than normal populations of fungi in their guts.
These patients often go on to develop strong antibody responses against mannan, which is a molecule that is common to a wide range of fungal species. However, researchers noticed that the healthy controls in these studies also had some level of anti-fungal antibodies. They say that there was no actual evidence for fungal infections in the healthy individuals that they examined. This made them think about the possible function of those antibodies.
The research team developed a platform that allowed them to determine which gut fungi are targeted by antibodies in the blood of individual patients. They noticed a strong response against the yeast Candida albicans. In mice experiments, researchers saw that if they colonise the animals' guts with Candida albicans, it caused them to develop antibodies against the fungus in their bloodstreams, even though they didn't develop blood-borne fungal infections. Instead, the animals' immune cells appeared to transport fungal antigens to the spleen, stimulating the production of circulating antibodies in the bloodstream. Those fungi just educate that immune response.
Many people have a suppressed immune system. This is especially true for patients of organ transplant and cancer patients. For them, fungi in the gut can invade the bloodstream and cause life-threatening infections. The researchers of the above-mentioned study mimicked this process by treating mice with immunosuppressive drugs.
When a Candida species colonizes the gut of these mice, the fungus moves into the bloodstream, causing a fatal infection. Treating the mice with purified anti-fungal antibodies from donor animals protected the immunosuppressed mice from these infections. The same strategy worked against infection with either Candida albicans or the emerging pathogenic yeast Candida auris, which has become a major cause of fungal disease in immunosuppressed patients and the elderly in recent years.
Researchers also looked at serum from patients with mutations in a gene called CARD9. This mutation affects a critical adapter protein in the immune system, leaving the affected individuals susceptible to severe fungal infections. They found that the serum of these patients lacked the anti-fungal antibodies normally seen in serum of patients without this mutation. Experiments in mice confirmed an essential and specific role for CARD9 in priming the production of anti-fungal antibodies.
The results suggest that normal intestinal fungi such as Candida albicans may function as a kind of intestinal vaccine against fungal infection in healthy people, by inducing the production of bloodborne antibodies that can target multiple species of potentially pathogenic fungi. When those fungi do enter the bloodstream, the antibodies bind them and target them for destruction by cells of the immune system. In patients with suppressed immunity, the anti-fungal antibodies may decline, leaving them vulnerable to fungal infection. New therapies that involve either stimulating the production of anti-fungal antibodies, or injecting such purified antibodies directly into patients' bloodstreams, could potentially help combat these increasingly common infections.
(With inputs from Agencies)
