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:6/23/2017)... ... June 23, 2017 , ... ... and related services to families and business owners in and around Lackawanna County, ... benefit senior citizens in the area. , Meals on Wheels of NEPA provides ...
(Date:6/22/2017)... ... June 22, 2017 , ... Branches, Inc. has been partnering with ... grant funding to support its programs focused on providing opportunity to low-income families and ... grant by the Foundation of $15,000 to support its , Climb to College & ...
(Date:6/22/2017)... ... June 23, 2017 , ... Despite its pervasiveness, many physicians are unfamiliar ... integrate basic science with clinical practice. Now, however, a timely review has been published ... insight into the etiology of NeuP and educating preclinical scientists on its diagnosis and ...
(Date:6/20/2017)... , ... June 20, 2017 , ... ... announced today that Claritas Capital, a Nashville-based private equity firm, has invested $3.35 ... expansion plans for some time, and Claritas Capital offers the smart money, speed ...
(Date:6/20/2017)... ... June 20, 2017 , ... Hayes, ... published a new eBook titled “ 5 Questions to Ask Before Entering the ... on the Genetic Test Evaluation (GTE) team, the book explores the various types ...
Breaking Medicine News(10 mins):
(Date:6/14/2017)... Calif. , June 14, 2017 The ... the City of Fremont and ... of the bio-pharma industry in California ... technology, enabling executive networking, and fostering workforce development. The ... development and growth of start-ups, as well as small ...
(Date:6/12/2017)... , June 12, 2017 Kineta, Inc., a ... announced Kineta Vice President of R&D and Head ... the Pandemic Preparedness for the Northwest and Beyond ... held on June 14, 2017 from 8:30-10:30 AM PDT at ... Dr. Bedard will be joined by ...
(Date:6/9/2017)... AirXpanders, Inc. (ASX: AXP) (AirXpanders or Company), ... sale and distribution of the AeroForm® Tissue Expander System, ... commercial roll-out in the United States ... hundred (100) medical institutions and health systems, located throughout ... alternative for women who choose reconstructive surgery following a ...
Breaking Medicine Technology: