Genetic Target To Fight Infections

Genetic Target To Fight Infections

Genetic Target To Fight Infections

Hospital patients are threatened with fungal infection that are proven difficult to combat, but scientists have unlocked evidence that could lead to more effective treatment. The Ohio State University researchers are the first to identify a potential gene-based approach to increasing the immune response to the fungus Candida albicans. This can find its way into the bloodstream and vital organs that includes the kidneys. A test of a potential treatment approach in mice rescued them from death.

Candida infection is one of the leading causes of bloodstream infections of hospital-acquired bloodstream infections. This infection has a mortality rate ranging from 45 to 75%.

Cancer Patients Are Susceptible To Candida

Those patients, especially with cancer who receive chemotherapy and those with an organ transplant who received immunosuppressive treatment and had all been catheterized, are highly susceptible to these infections and can be lethal to the patient.

According to lead researcher Jian Zhang, associate professor of microbial infection and immunity, said they have found a potential way to manipulate the immune system to treat invasive, life-threatening cases that are resistant to treatment. Their research can be found in the journal Nature Medicine.

At the beginning of their study they knew that a group of molecules called C-type lectin receptors played a key role in controlling fungal infections. With healthy individuals whose bodies fight off the infection, the receptors detect the bad fungal cells and set off a chain of events that kicks the immune system into action. Previously the researchers knew that a gene called CBLB played a role in the process, but it wasn’t clear just what the role was.

The group performed tests of human cells in petri dishes and in mice, and was able to pinpoint what CBLB does. Two proteins (dectin 1 and 2) are targeted, which sends messages crucial for a robust immune response. This proteins’ job is to recognize the carbohydrates that line the fungi’s cell wall and kick off an appropriate response by immune cells. CBLB’s role is to guard against a too-intense immune response to the Candida infection if it were in a perfect scenario. Inflammation is tamped down and prevents tissue damage by moving the proteins to a molecular trash can.

In the weak hospitalized patients with bloodstream infections, CBLB stands in the way of an optimal immune response and the immune response is dampened to a level that no longer protects them against fungal invaders.

The research confirmed that if they knocked out CBLB function through eliminating or deactivating it, the animals’ immune systems waged a greater battle against the yeast. The antifungal response will be accelerated so you can clear the infection, if you can downregulate or inactivate the gene. This was confirmed in mice by injecting small interference RNA in an attempt to interrupt CBLB expression. When they did it this way they could actually recue the mice from death.

This should open the door to further research in exploring the possibility of a gene-based treatment for humans that might target CBLB to allow patients’ immune systems to tackle the invader. The National Institutes of Health supported this research.
-Dr Fredda Branyon

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