DEC 23, 2016 10:55 AM PST

Rare Mutation Increases Vulnerability to Fungal Infections

WRITTEN BY: Kara Marker

A new study identified an important mechanism in the innate immune response against fungal infections, explaining why specific genetic variations make some people more vulnerable to fungal infections than others.

Credit: A. Heddergott / TUM

 Fungal infections are especially dangerous for immunocompromised individuals like those who are receiving chemotherapy or who suffer from autoimmune diseases. In contrast to the adaptive immune system that changes and conforms to the environment one lives in, the intricated, detailed innerworkings of the innate immune system are essentially set in stone genetically before birth.

From the Technical University of Munich, scientists began their study of the innate immune response to certain fungal infections. Past research findings provided some background knowledge of how the immune system uniquely targets fungal infections. First, the immune attack begins with protein elements called C-type lectin receptors found in blood and tissue cells. C-type lectin receptors are programmed to recognize fungal cells by molecules on their cell surface. This recognition then triggers a signaling pathway that recruits the proper immune cells to the site of infection.

Another protein, called CARD9, was also noted in past research as a key player in the signaling pathway required for the body to trigger an immune response to kill fungal cells, but scientists still were not sure of any details of CARD9’s involvement.

In the new study, scientists discovered three precursor proteins that need to be activated before CARD9 can get to work: Vav1, Vav2, and Vav3. If all three Vav proteins were to be deactivated due to a genetic mutation, the individual with the genetic alteration would be especially prone to fungal infections, even with functional CARD9 present.

“The functions of the Vav proteins were understood mainly as part of the acquired or adaptive immune system,” explained first author Dr. Susanne Roth. “Their functions in the innate immune response remain largely unexplored.”

“We also assume that the immune response to fungal infections is not the only place where the Vav protein dependent innate immune mechanisms we have discovered play a role,” said Jurgen Ruland.

Roth and her team used patient data to demonstrate the importance of Vav proteins for innate immunity. They observed one genetic variation appearing particularly common among a population of people suffering from candidiasis, a yeast infection. The variation causes Vav3 protein to be slightly malformed.

“We can now develop strategies to directly influence the signal pathway,” Ruland said. “If we are able to switch it on by artificial means, this could be used for vaccinations.”

The present study was recently published in the journal Cell Reports.

Source: Technical University of Munich

About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
You May Also Like
OCT 03, 2018
Immunology
OCT 03, 2018
Let's Cut the Brakes on the Immune System
Two laureates receive Nobel Prize for their work regarding immune checkpoint therapy...
NOV 15, 2018
Drug Discovery
NOV 15, 2018
Anti-inflammatory Drug Works Like an Inhibitor
At Karolinska Institutet in Sweden, a team of scientists from multiple disciplines have worked together to develop an inflammation inhibitor. The new anti-...
NOV 20, 2018
Immunology
NOV 20, 2018
Survival of the SCID Patient
A team of scientists reviewed over 600 SCID patients medical records to establish the relationship between genetics and survival rates....
DEC 08, 2018
Health & Medicine
DEC 08, 2018
Chronic Fatigue: Where Are We in Our Understanding?
  Ask anyone who suffers from an autoimmune disease or fibromyalgia about the most challenging aspect of their condition, and the answer will be unani...
DEC 15, 2018
Cell & Molecular Biology
DEC 15, 2018
HIV Vaccine Successful in Non-human Primates
Researchers have been trying to create a vaccine for HIV, the virus that causes AIDS, for decades....
JAN 15, 2019
Immunology
JAN 15, 2019
Stem Cells: Is a Clean Slate Always a Better Start?
A new USC and Stanford study, conducted in mice, deepens the mystery, showing that successfully transplanted stem cells don't behave "normally" as in a healthy person without a transplant....
Loading Comments...