Navigation Links
Persistent bacterial infection exploits killing machinery of immune cells
Date:11/2/2008

A new study reveals an important and newly discovered pathway used by disease-causing bacteria to evade the host immune system and survive and grow within the very cells meant to destroy them. This discovery may lead to new treatments and vaccines for tuberculosis (TB) and certain other chronic bacterial and parasitic infections.

The research, supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is the work of the laboratories headed by Peter Murray, Ph.D., at St. Jude Children's Research Hospital in Memphis, Tenn., and Thomas Wynn, Ph.D., of the Laboratory of Parasitic Diseases at NIAID. Their findings appear in the November issue of Nature Immunology.

Clearing the body of disease-causing bacteria is the job of specialized white blood cells called macrophages. The word "macrophage" means "big eater" in Latin and that is just what these cells are--they gobble up cell debris, infected cells and disease-causing bacteria found in the body. To help them digest and destroy what they eat, macrophages make compounds that in most cases kill pathogens. One of these chemicals is the free radical nitric oxide (NO).

However, some harmful bacteria, known as intracellular pathogens, live inside cells and can even survive and replicate within macrophages, somehow inhibiting or escaping killing by NO. One natural NO inhibitor made by macrophages is the enzyme arginase. Arginase steals and degrades the material required to make NO, therefore limiting how much NO is made.

"The bacteria designed to live inside the cell are highly adapted to their environment," says Dr. Murray. "We wanted to determine just how intracellular bacteria were turning on the genes that make arginase, thereby controlling the expression of NO and escaping killing by macrophages."

The research team discovered that intracellular pathogens increase levels of arginase, thereby reducing the amount of NO the macrophages produce, enabling intracellular pathogens to survive. The presence of persistent intracellular bacteria is particularly harmful to people with compromised immune systems, such as people with HIV or cancer, who often contract chronic bacterial and parasitic infections.

To test the significance of arginase production induced by the intracellular bacterium that causes TB, Mycobacterium tuberculosis, the researchers generated mice lacking the arginase gene in their macrophages (arginase knockout mice). After infecting the arginase knockout mice with the TB bacteria, they observed that the mice had fewer bacteria and higher levels of NO in their lungs.

The researchers then infected arginase knockout mice with an intracellular parasite that causes toxoplasmosis, a disease that also is controlled by NO. They observed that mice lacking arginase had higher survival rates than mice that produced arginase.

However, when knockout mice were infected with bacteria that are not killed by NO, the lack of arginase did not affect the macrophages' ability to clear the infection.

"Although NO was named 'molecule of the year' in 1992 by Science Magazine and studied as an important part of the immune response to bacterial infections, arginase, its counterbalance, was widely ignored by the immunology community," comments Dr. Wynn. "This work suggests that targeting arginase may be helpful in treating chronic, intracellular bacterial and parasitic infections."

Drs. Murray and Wynn hope to next determine what other parts of the immune system are affected when arginase is blocked.


'/>"/>

Contact: Julie Wu
wujuli@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
Source:Eurekalert

Related medicine news :

1. First evidence that prenatal exposure to famine may lead to persistent epigenetic changes
2. New Webcast Going for Gold to Educate on Importance of Healthy Diet In Persistent Chronic Pain Management
3. Study analyzed SYMBICORT in children with persistent asthma
4. Persistent Insomnia Leads to Depression in Young Adults
5. Study Analyzed Long-Term SYMBICORT(R) Use in Children With Persistent Asthma
6. Study identifies which men are likely to have persistent prostate cancer
7. Want to Raise a Fruit-and-Veggie Lover? Be Persistent
8. Meniscal damage and the development of persistent knee pain
9. Comment Regarding Congregation for the Doctrine of Faith Clarification Concerning Nutrition and Hydration for Patients in a Persistent Vegetative State
10. Investigators uncover intriguing clues to why persistent acid reflux sometimes turns into cancer
11. Bacterial peptide provides new insight into common tumor suppressor
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... LUIS OBISPO, Calif. (PRWEB) , ... October 13, 2017 , ... ... Alzheimer’s or dementia. However, many long-term care insurance companies have a waiver for care ... is the 90-day elimination period, when the family pays for care, is often waived, ...
(Date:10/13/2017)... ... 13, 2017 , ... Global Healthcare Management’s 4th Annual Kids Fun Run brought ... This free event, sponsored by Global Healthcare Management’s CEO, Jon Letko, is aimed at ... towards children of all ages; it is a non-competitive, non-timed event, which is all ...
(Date:10/13/2017)... ... October 13, 2017 , ... ... Software Development, has been awarded a contract by the Center for Medicare and ... aims to accelerate the enterprise use of Agile methodologies in a consistent and ...
(Date:10/12/2017)... ... 12, 2017 , ... First Healthcare Compliance (FHC), an industry ... a range of technology and learning solutions at the 68th Annual American Healthcare ... be held October 14–18, 2017 at the Mandalay Bay Resort in Las Vegas, ...
(Date:10/12/2017)... ... October 12, 2017 , ... The company has developed ... consumer and regulatory authorities worldwide. From Children’s to Adults 50+, every formula has ... highest standard. , These products are also: Gluten Free, Non-GMO, Vegan, Soy ...
Breaking Medicine News(10 mins):
(Date:10/12/2017)... , Oct. 12, 2017 West ... in innovative solutions for injectable drug administration, today announced ... the market opens on Thursday, October 26, 2017, and ... results and business expectations at 9:00 a.m. Eastern Time. ... or 253-336-8738 (International). The conference ID is 94093362. ...
(Date:10/11/2017)... 11, 2017  True Health, a leader in ... effort during National Breast Cancer Awareness month to ... Research recently ... that more than 10 million American women are ... BRCA1 or BRCA2 and have not had testing. These ...
(Date:10/10/2017)... 10, 2017   West Pharmaceutical Services, Inc. ... injectable drug administration, today shared the results of a ... improving the intradermal administration of polio vaccines. The study ... in May 2017 by Dr. Ondrej Mach , ... Health Organization (WHO), and recently published in the journal ...
Breaking Medicine Technology: