About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

New Pathway That Triggers Septic Shock Identified

by Sheela Philomena on September 13, 2013 at 11:51 AM
Font : A-A+

 New Pathway That Triggers Septic Shock Identified

A sensor pathway inside the cells that triggers septic shock has been identified by scientists. These internal sensors are like motion detectors inside a house; they trigger an alarm that signals for help — a response from the immune system. This research, published in the Sept. 13, 2013 issue of the journal Science, indicates that both exterior and interior sensors work together to detect the same component of bacterial cell membranes, a molecule called lipopolysaccharide or LPS.

By showing how the immune system distinguishes between suspicious activity and real threats, the study could lead to new therapies for septic shock — when the immune system overreacts to a bacterial infection to such an extent that it causes more harm than good.

Advertisement

"During the defense against an infection you want to be able to differentiate between the bacteria that stay on the outside of the cell and the ones that get inside," said senior study author Edward A. Miao, MD, PhD, assistant professor of microbiology and immunology. "You can think of the exterior sensors as a yellow alert; they tell us that bacteria are present. But these bacteria could either be simple ones in the wrong place, or very dangerous ones that could cause a serious infection. The interior sensors act as a red alert; they warn us that there are bacteria with ill intent that have the genetic capacity to invade and manipulate our cells."

The body responds to a bacterial infection by increasing blood vessel permeability near the area under attack, which allows immune system cells to leave the bloodstream and seek and destroy the bacteria. Fluid also leaks into the area surrounding the infection, causing characteristic swelling. This is beneficial in fighting infection, but when the infection gets out of hand and these immune response occur throughout the body, blood pressure plummets, overtaxing the heart and leading to organ failure and often death. This increasingly prevalent syndrome, known as septic shock, afflicts over 750,000 people each year in the United States at a cost of nearly $17 billion.
Advertisement

About half of the cases of septic shock are caused by bacteria that produce LPS, also known as endotoxin. In fact, much of what is known about endotoxic shock comes from studying animals injected with high doses of LPS. For example, previous studies pinpointed the role of the Toll-like receptor 4 gene (TLR4) as a sensor on the outside of cells; mice without that gene resisted endotoxic shock.

In a study published in January 2013, also in the journal Science, Miao and his colleagues showed that a sensor called caspase-11 sounds an alert when bacteria enter a cell. However, it wasn't clear which of the thousands of molecules that make up a bacterial cell triggers that new sensor.

In the current study, Miao and his colleagues investigated which bits of foreign material were being detected. They took apart and delivered different chunks of bacteria into the cytoplasmic compartment inside the cell. To their surprise, they found that the caspase-11 sensor inside the cell was detecting the same molecule, LPS, as the TLR4 sensor outside the cell. The researchers wondered whether there was a link between these two sensors.

Through a number of experiments in animal models of sepsis, Miao's team showed that the exterior and interior alarms work together through a two-step defense mechanism: LPS is first seen on the outside of the cell by TLR4, which sets the interior caspase-11 alarm into a watchful state. At very high doses, the LPS crosses into the cell, tripping the caspase-11 alarm. The end result is the generation of the red alert signal, which causes the cell to explode, a form of cell death called pyroptosis. During an infection, the immune system essentially burns the house down around the invading bacteria, depriving it of a place to replicate, and exposing it to more potent immune defenses. During sepsis, however, too much fire leads to the onset of shock.

Miao says that figuring out how these two sensors get activated in response to a bacterial infection could help researchers develop new ways of preventing or treating septic shock, a condition that kills about half its victims.

"The septic shock we see in patients is probably a lot more complicated than what we see in this experimental system," said Miao. "The next question we need to ask is whether these same sensors are going off in people with septic shock, and if so, is there a way to block them so we can keep patients from dying."

Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Advertisement
News Category
What's New on Medindia
Woman with Rare Spinal Cord Defect from Birth Sues Doctor
Toothache
World AIDS Day 2021 - End Inequalities, End AIDS
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Septicemia 

Recommended Reading
Septicemia
Septicemia or sepsis is a serious illness wherein a patient develops symptoms due to presence of ......
Study Sheds Light on How Stomach Bug Manages to Beat Immune System to Cause Infection
A new study sheds light on how Helicobacter pylori bacteria, which causes a life-long stomach ......
Study Sheds Light on How Immune System Fights Off Invading Pathogens
Researchers are currently tracking previously unknown movements of a set of specialized cells to ......
Source of Infection Affects Hospital Mortality in Septic Shock Patients in the ICU: Study
According to a new study from researchers in Canada, in ICU patients who have septic shock, the ......

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use