• ACVC Callout
News
ICViewExpert PerspectivesMedical World NewsVideosWebinars
Conference
Infection Control TodaySupplements And Featured Publications
CME/CEJob BoardPartnersSponsoredWhitepapers
Print SubscriptioneNewsletter
Educator of the Year Nomination FormEducator of the Year Official RulesEducator of the Year
Advanced Technology
Bug of the Month
COVID-19
Environmental Services
HAIs
Hand Hygiene
Long-Term Care
Operating Room
Personal Protective EquipmentPersonal Protective Equipment
Prevention
Sterile Processing
Surface Disinfection
Vascular Access
Spotlight -
  • Expert Perspectives on Personal Protection Guidelines and Standardization Practices
  • Bug of the Month
Advanced Technology
Bug of the Month
COVID-19
Environmental Services
HAIs
Hand Hygiene
Long-Term Care
Operating Room
Personal Protective EquipmentPersonal Protective Equipment
Prevention
Sterile Processing
Surface Disinfection
Vascular Access
    • News
    • Conference
Advertisement

Genes Linked to Sepsis-Related Death are Identified in Mouse Model

July 23, 2019
Article

Sepsis is a life-threatening condition that occurs when the body’s immune response to infection spirals out of control. Bacteria in the bloodstream trigger immune cells to release powerful molecules called cytokines to quickly activate the body’s defenses.

Sepsis is a life-threatening condition that occurs when the body’s immune response to infection spirals out of control. Bacteria in the bloodstream trigger immune cells to release powerful molecules called cytokines to quickly activate the body’s defenses. Sometimes the response goes overboard, creating a so-called “cytokine storm” that leaves people feverish or chilled, disoriented and in pain. In severe cases, it can lead to multi-organ failure and death.

Now, researchers at Washington University School of Medicine in St. Louis have found a set of genes that help cells survive exposure to cytokines. The genes are involved in disposing of cellular waste, a process known as autophagy. Mice that lack key autophagy genes are more likely to die from sepsis, the study shows. The findings raise the possibility that enhancing autophagy could potentially lead to treatments for the deadly condition.

“When we recognize signs of sepsis in patients, we prescribe antibiotics and fluids, but we lack therapies to protect patients from the direct effects of the cytokine storm,” said first author Anthony Orvedahl, MD, PhD, an instructor in pediatric infectious diseases. “Our research indicates that if we could modulate autophagy levels in cells, we might be able to promote cell survival and resistance to the cytokine storm, which may ultimately help people survive sepsis.”

The study is published online the week of July 22 in Proceedings of the National Academy of Sciences.

Sepsis is a medical emergency and even with prompt medical care, about 15 percent of people do not survive, while many survivors experience longstanding complications. Orvedahl – along with colleagues including senior author Herbert “Skip” Virgin, IV, MD, PhD, now at Vir Biotechnology, and co-author Gary A. Silverman, MD, PhD, the Harriet B. Spoehrer Professor and head of the Department of Pediatrics – set out to find what protects cells from dying during a cytokine storm.

The researchers looked at the effects of interferon gamma, a cytokine that activates immune cells’ ability to kill bacteria but can also trigger cell death. By systematically inactivating one gene at a time from immune cells in a dish before treating them with interferon gamma, the researchers discovered that cells need a full complement of autophagy genes to survive exposure to the potent cytokine. Further experiments revealed that a second cytokine, called tumor necrosis factor, was also critical for the accelerated cell death in this system.

“Autophagy is like cleaning the house, getting rid of all the junk inside the cell,” Orvedahl said. “If unwanted things start to accumulate via a defect in this recycling system, it’s like a tinderbox waiting for a spark. We don’t yet know the exact material involved, but we think something builds up and makes cells more vulnerable to dying when they encounter these inflammatory cytokines.”

The importance of autophagy on cell survival suggests that the process may also be crucial for the survival of animals – and people – in the midst of a cytokine storm. To find out, the researchers studied four strains of genetically modified mice that lacked one of four autophagy genes in their immune cells, as well as mice with intact autophagy genes. They injected mice with tumor necrosis factor, which is thought to drive the cytokine storm in people. The mice whose autophagy systems were crippled by the absence of important autophagy genes got sick faster and were more likely to die.

Chemical compounds that enhance or block autophagy are already being studied by researchers focused on cancer, cardiovascular disease and other conditions. Therapies that suppress autophagy may increase the risk of sepsis, Orvedahl said. Further, he cautioned that more research is needed before doctors can evaluate whether boosting autophagy is a viable strategy for treating sepsis.

“We can’t say for sure that autophagy activation would be protective,” Orvedahl said. “We just showed that if mice lack autophagy, they are sicker and more likely to die. But we think that a better understanding of these processes could lead to attractive targets for developing more effective ways to treat sepsis.”

Washington University in St. Louis

Related Videos
Set of white bottles with cleaning liquids on the white background. (Adobe Stock 6338071172112 by zolnierek)
Medical investigators going over data. (AdobeStock 589197902 by Wasan)
CDC logo is seen on a laptop. (Adobe Stock 428450603 by monticellllo)
Association for the Health Care Environment (Logo used with permission)
COVID-19 germs, fungi, bacteria objects. (Adobe Stock 584704860 by chawalit)
Ambassador Deborah Birx, , speaks with Infection Control Today about masks in schools and the newest variant.
mRNA technology  (Adobe Stock 485886181 by kaptn)
Ambassador Deborah Birx, MD
Woman lying in hospital bed (Adobe Stock, unknown)
Related Content

Low Vaccination Concerns Highlight Need for Fall and Winter 2023 Vaccination Campaigns

September 28th 2023

Evolving Symptomatology: Respiratory Viruses in the Era of COVID-19 Variants

September 27th 2023

I’m Not Just an Infection Preventionist

September 26th 2023

Poll: What Minimum Educational Requirement Should Infection Preventionists Have?

September 25th 2023

How to Prepare For Possible “Tripledemic” of RSV, Influenza, and SARS-CoV-2

September 25th 2023

Weekly Rounds: Data-Driven Action Against COVID-19, Emerging Pathogens, HIV Vaccine Trials Begin, and More

September 22nd 2023

Low Vaccination Concerns Highlight Need for Fall and Winter 2023 Vaccination Campaigns

September 28th 2023

Evolving Symptomatology: Respiratory Viruses in the Era of COVID-19 Variants

September 27th 2023

I’m Not Just an Infection Preventionist

September 26th 2023

Poll: What Minimum Educational Requirement Should Infection Preventionists Have?

September 25th 2023

How to Prepare For Possible “Tripledemic” of RSV, Influenza, and SARS-CoV-2

September 25th 2023

Weekly Rounds: Data-Driven Action Against COVID-19, Emerging Pathogens, HIV Vaccine Trials Begin, and More

September 22nd 2023

Low Vaccination Concerns Highlight Need for Fall and Winter 2023 Vaccination Campaigns

September 28th 2023

Evolving Symptomatology: Respiratory Viruses in the Era of COVID-19 Variants

September 27th 2023

I’m Not Just an Infection Preventionist

September 26th 2023

Poll: What Minimum Educational Requirement Should Infection Preventionists Have?

September 25th 2023

How to Prepare For Possible “Tripledemic” of RSV, Influenza, and SARS-CoV-2

September 25th 2023

Weekly Rounds: Data-Driven Action Against COVID-19, Emerging Pathogens, HIV Vaccine Trials Begin, and More

September 22nd 2023
Related Content
Advertisement

In this photo illustration, National Foundation for Infectious Diseases logo is seen displayed on a smartphone    (Adobe Stock 346303670 By Игорь Головнёв)

Low Vaccination Concerns Highlight Need for Fall and Winter 2023 Vaccination Campaigns

September 28th 2023
Article

Cases of COVID-19, RSV, and influenza are expected to rise this fall and winter season; yet, the number of people who plan on getting the vaccines for each of the infections remains low, according to the NFID announcement today.


COVID-19 germs, fungi, bacteria objects.   (Adobe Stock 584704860 by chawalit)

Evolving Symptomatology: Respiratory Viruses in the Era of COVID-19 Variants

September 27th 2023
Article

As COVID-19 restrictions eased up, other respiratory viruses began circulating alongside SARS-CoV-2. It's crucial to identify cases and understand the symptoms of these infections to track the evolution of the virus and what health care workers should look out for.


An infection preventionist taking off her mask. (Adobe Stock, unknown)

I’m Not Just an Infection Preventionist

September 26th 2023
Article

Infection preventionists (IP) can come from many different backgrounds. This is 1 opinion from 1 very successful IP who doesn't have an RN or a BSN and the bullying that sometimes occurs.


(Adobe Stock FILE #:  56169337 by thinglass)

Poll: What Minimum Educational Requirement Should Infection Preventionists Have?

September 25th 2023
Article

Many infection preventionists (IPs) disagree on the minimum requirement to have the IP position. Let Infection Control Today know your opinion. Answer this poll, and send your thoughts to Senior Editor Tori Whitacre Martonicz at tmartonicz@mjhlifesciences.com.


Influenza, RSV, and COVID-19 (AdobeStock_249346161, AdobeStock_538653843,AdobeStock_471755796)

How to Prepare For Possible “Tripledemic” of RSV, Influenza, and SARS-CoV-2

September 25th 2023
Article

The interaction between the respiratory viruses SARS-CoV-2, influenza, and RSV, poses ongoing challenges. Personal protective measures, testing, and vaccination are critical components of our strategy to mitigate the impact of these viruses.


weekly rounds with infection control today

Weekly Rounds: Data-Driven Action Against COVID-19, Emerging Pathogens, HIV Vaccine Trials Begin, and More

September 22nd 2023
Article

Take 5 minutes to catch up on Infection Control Today®’s highlights for the week ending September 24, 2023.

Advertise
About Us
Editorial Board
Contact Us
Job Board
Terms and Conditions
Privacy
Do Not Sell My Personal Information
Contact Info

2 Clarke Drive
Cranbury, NJ 08512

609-716-7777

© 2023 MJH Life Sciences

All rights reserved.
Home
About Us
News