Featured Research

from universities, journals, and other organizations

Killing Bacteria Isn't Enough To Restore Immune Function After Infection

Date:
September 12, 2008
Source:
UT Southwestern Medical Center
Summary:
A bacterial molecule that initially signals to animals that they have been invaded must be wiped out by a special enzyme before an infected animal can regain full health, researchers at UT Southwestern Medical Center have found.

A bacterial molecule that initially signals to animals that they have been invaded must be wiped out by a special enzyme before an infected animal can regain full health, researchers at UT Southwestern Medical Center have found.

Using a genetically engineered mouse model, the team found that simply eradicating the infection-causing bug isn't enough to restore an animal's immune function. Lipopolysaccharide, or LPS, the dominant bacterial "signal" molecule that heralds the invasion, must also be inactivated. The findings are to appear online Sept. 11 in Cell Host & Microbe.

"We think this is the first evidence that killing the causative agent of a bacterial infection isn't enough for an animal to recover fully," said Dr. Robert Munford, professor of internal medicine and microbiology, and senior author of the study. "You've got to get rid of this molecule that the host is responding to or else its immune system remains suppressed."

By sensing and responding to LPS, animals mobilize their defenses to attack and kill the bacteria. This immune response also causes inflammation in the host. For a few days after the infection begins, however, an animal's ability to sense the bacteria is turned down, presumably to prevent further inflammation. In the current study, the researchers found that mice didn't recover from this "tolerant" period unless the LPS was inactivated by acyloxyacyl hydrolase, an enzyme discovered in 1983 by Dr. Munford and Dr. Catherine Hall, now an assistant professor of internal medicine at UT Southwestern.

Dr. Mingfang Lu, instructor of internal medicine and lead author of the current study, said the team also found that prolonged tolerance was immunosuppressive, reducing the animal's ability to stave off another bacterial infection.

Dr. Lu said that how long an animal remains in this tolerant state varies from animal to animal. "But mice that can't make the enzyme acyloxyacyl hydrolase seem to stay tolerant forever, leaving them unable to fight additional infections," she said.

For the study, researchers injected LPS or a common bacterium that makes LPS into the abdomens of two types of mice: ones that could produce the acyloxyacyl hydrolase enzyme and ones that could not. Two weeks later they injected the mice with a deadly strain of Escherichia coli – which can cause loss of water and salts, damage to blood vessels, and bleeding in humans – to gauge how prolonged tolerance influences the animal's internal defense mechanisms.

Though almost all of the mice with the enzyme survived, 90 percent of those without the enzyme died. "Being tolerant, or unable to respond normally, made them more susceptible to the E coli we injected them with," Dr. Lu said.

Dr. Munford said they don't have any evidence that this finding is applicable to humans, who also make the enzyme, but it is possible.

"One theory is that there is variability among humans in the production of acyloxyacyl hydrolase," he said. "We don't know this yet, but if it's true, then the presence or absence of the enzyme might contribute to the length of immunosuppression after serious bacterial infections. It might even be reversible if we could provide the enzyme or figure out a way for people to make more of it."

The team's next step is to investigate further how LPS continues to stimulate the host's immune cells for such long periods of time if it does not get degraded. They also hope to use this animal model to understand better on a molecular scale exactly what happens during post-infection immunosuppression.

Other UT Southwestern researchers involved in the study were Dr. Alan Varley, assistant professor of internal medicine, and John Hardwick, former research associate in internal medicine. Shoichiro Ohta, a researcher from Saga Medical School in Japan, also contributed to the study.

The work was supported by the National Institute of Allergy and Infectious Diseases.


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

UT Southwestern Medical Center. "Killing Bacteria Isn't Enough To Restore Immune Function After Infection." ScienceDaily. ScienceDaily, 12 September 2008. <www.sciencedaily.com/releases/2008/09/080910133932.htm>.
UT Southwestern Medical Center. (2008, September 12). Killing Bacteria Isn't Enough To Restore Immune Function After Infection. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2008/09/080910133932.htm
UT Southwestern Medical Center. "Killing Bacteria Isn't Enough To Restore Immune Function After Infection." ScienceDaily. www.sciencedaily.com/releases/2008/09/080910133932.htm (accessed July 30, 2014).

Share This




More Health & Medicine News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Generics Eat Into Pfizer's Sales

Generics Eat Into Pfizer's Sales

Reuters - Business Video Online (July 29, 2014) Pfizer, the world's largest drug maker, cut full-year revenue forecasts because generics could cut into sales of its anti-arthritis drug, Celebrex. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins