JAN 30, 2019 5:43 PM PST

Immune Messaging to Zap Sepsis

WRITTEN BY: Nicholas Breehl

Small infections can be fatal: Millions of people die each year from sepsis, an overreaction of the immune system. A new immune signaling molecule, designed by a research team from the Technical University of Munich (TUM), now provides the basis for potential new approaches in sepsis therapy.

The numbers are alarming: According to estimates by the World Health Organization (WHO), around six million people die every year from sepsis. The disease, popularly called "blood poisoning," starts typically with a simple infection.

If this triggers an excessive reaction of the immune system, the body's tissue can be attacked and damaged. The overreaction eventually leads to a life-threatening collapse of the body's defenses. In Germany alone, more people die of sepsis than of AIDS, colon cancer and breast cancer combined.

Researchers around the world are on the search for new therapies -- so far in vain. An interdisciplinary team from the fields of structural biology, immunology and cell biology has now, for the first time, successfully produced a protein that could balance the overshooting immune response.

The language of immune cells

In their work, the scientists were inspired by evolution: mice are well protected from sepsis by their immune systems. Here, interleukins -- messengers, that mediate communication between the cells of the immune system -- play a crucial role.

"The interleukins are the vocabulary with which immune cells communicate," explains Matthias Feige, Professor of Cellular Protein Biochemistry at the Technical University of Munich. The cells form these messenger molecules according to a precise blueprint of individual amino acids. Their arrangement determines, which three-dimensional structure an interleukin adopts and, consequently, which information it transmits.

Humans and mice have similar, yet different vocabularies. The researchers discovered one striking difference in interleukin-27-alpha. This molecule can be released by cells of the mouse immune system -- but not by human cells -- and regulates immune cell function.

"Using computer models and cell biological experiments, we discovered that a single structurally important amino acid defines whether interleukin-27-alpha is released by cells of the immune system," explains Stephanie Müller, the first author of the study. "That gave us an idea about how we can engineer novel human interleukin proteins that are released by cells so that we can produce them biotechnologically."

Proteins with new functions from the laboratory

The team then prepared the modified interleukin in the laboratory and tested its biological functions -- with very encouraging results: The engineered messenger molecule is recognized by human cells. First analyses suggest that it can indeed balance an overreaction of the immune system, making it a promising candidate for sepsis therapy.

"Our approach allowed us to rationally extend the language of immune cells by engineering a key signaling molecule. This provides us with an opportunity to modulate the reaction of immune cells in a targeted manner. Such a finding was only possible thanks to the close collaboration with immunologists and clinicians from TUM, the Université Sorbonne in Paris and the Helmholtz Zentrum Muenchen," says Feige. A patent for the new protein is already pending.

Sources: Science Daily, PNAS, YouTube

About the Author
You May Also Like
MAR 22, 2021
Immunology
Gene Mutation Keeps Tumors "Cold"
MAR 22, 2021
Gene Mutation Keeps Tumors "Cold"
Immunologists have identified a mechanism through which an oncogene mutation shields pancreatic tumors from immune cells ...
APR 22, 2021
Immunology
Healthy, Young People Are Getting Reinfected With COVID
APR 22, 2021
Healthy, Young People Are Getting Reinfected With COVID
If you’re young and healthy and you’ve had COVID, your body will produce protective antibodies that guard yo ...
MAY 12, 2021
Health & Medicine
Researchers Discover a New Genetic Disease that Prevents Antibody Formation
MAY 12, 2021
Researchers Discover a New Genetic Disease that Prevents Antibody Formation
Doctors at the Children's Hospital of Philadelphia discovered a new genetic disease that prevents B cell development.
JUN 03, 2021
Immunology
Inhalable Anti-COVID Nanobodies Show Promising Results in Hamsters
JUN 03, 2021
Inhalable Anti-COVID Nanobodies Show Promising Results in Hamsters
Nanobodies are small fragments of monoclonal antibodies that from a therapeutic perspective are more stable and cheaper ...
JUN 11, 2021
Cannabis Sciences
Does Cannabis Interact with the COVID Vaccine?
JUN 11, 2021
Does Cannabis Interact with the COVID Vaccine?
As of June 10th 2021, 43% of people in the US aged 12 and over have been fully vaccinated for COVID-19, with 5 ...
JUN 24, 2021
Immunology
Gut-Healing Stem Cells to Treat HIV Infections
JUN 24, 2021
Gut-Healing Stem Cells to Treat HIV Infections
A new study has revealed how stem cells can be used to amplify immune responses to HIV, the virus that causes AIDS. The ...
Loading Comments...