Gamma interferon a wake-up call for stem cell response to infection

Jun 09, 2010

Most of the time, the body's blood-forming (hematopoietic) stem cells remain dormant, with just a few producing blood cells and maintaining a balance among the different types.

However, invading bacteria can be a call-to-arms, awaking the sleeping and prompting them to produce cells that fight the foreign organisms. The "bugler" that awakes the stem cells in this battle is gamma interferon, a front-line protein defender against bacterial infection, said researchers from Baylor College of Medicine in a report that appears in the current issue of the journal Nature.

"We are looking at the normal function of stem cells," said Dr. Margaret Goodell, professor of molecular and at BCM and director of the Stem Cells and Regenerative Medicine (STaR) Center. She is the report's senior author. "One of those is to respond to an infection."

Goodell and her colleagues knew that cells farther along in the differentiation process responded to infection, increasing the production of .

"We were sure there was a mechanism by which hematopoietic stem cells respond to infection, but it was not obvious," she said. They started their work with gamma interferon because they knew it played an important role in bacterial infection.

The collaboration and talents of two researchers in her laboratory - first co-authors Drs. Megan T. Baldridge and Katherine Y. King - facilitated the work with mice that led to this finding, said Goodell. Both are at BCM.

"I think our findings represent an exciting new avenue for studying hematopoiesis," said King. "By viewing the hematopoietic stem cell as the source of the immune system, we are finding fundamental ways in which the immune response affects bone marrow. This is the first time that anyone has extensively studied hematopoietic stem cells in the context of an in vivo model (a living organism) of infection."

"As a specialist in infectious diseases, I see many patients whose bone marrow no longer produces sufficient blood cells as a consequence of their infection. This is particularly relevant in chronic infections such as mycobacterial diseases (that include tuberculosis) and AIDS," said King. "Our studies lend insight into the causes of this decrease in bone marrow function during such infections, and I hope the work will someday lead to new therapies."

Studies in mice with a chronic or long-term infection called Mycobacterium avium show that a greater proportion of a particular subset of their cells called long-term hematopoietic (blood-forming) stem cells are active. Gamma interferon prompts this activity. Mice that lack gamma interferon have fewer of these stem cells active during infection.

These findings show that gamma interferon not only activates stem cells during infection, but also regulate stem cells in normal times, enabling them to maintain the types of that exist in proportion or homeostasis.

"Our model predicts that detected by sentinel immune cells stimulates the increased release of gamma interferon, which then travels through the blood stream to activate HSCs (hematopoietic stem cells) in the bone marrow, leading to expansion and mobilization of the immune progenitor pool (the cells that ultimately produce immune system cells)," the researchers wrote.

They found that sustained activity by the hematopoietic stem cells can lead to at least transient problems with the quality of the stem cells and their abilities to stimulate production of more .

"One of the most important things we found is the chronic infections (such as tuberculosis or HIV/AIDS) may be lead to exhaustion," said Baldridge. "We knew that a condition called anemia of chronic disease exists, and this could be one of the contributing factors."

Explore further: Infant cooing, babbling linked to hearing ability

Related Stories

Theory of single stem cell for blood components challenged

Mar 04, 2010

Components of the blood or hematopoietic system derive from stem cell subtypes rather than one single stem cell that gives rise to all the different kinds of blood cells equally, said scientists from Baylor College of Medicine ...

Molecule dictates how stem cells travel

Jan 14, 2006

U.S. researchers have defined a molecule that dictates how blood stem cells travel to the bone marrow and establish blood and immune cell production.

Protein key to control, growth of blood cells

Aug 13, 2008

New research sheds light on the biological events by which stem cells in the bone marrow develop into the broad variety of cells that circulate in the blood. The findings may help improve the success of bone marrow transplants ...

Recommended for you

Infant cooing, babbling linked to hearing ability

3 hours ago

Infants' vocalizations throughout the first year follow a set of predictable steps from crying and cooing to forming syllables and first words. However, previous research had not addressed how the amount ...

Developing 'tissue chip' to screen neurological toxins

4 hours ago

A multidisciplinary team at the University of Wisconsin-Madison and the Morgridge Institute for Research is creating a faster, more affordable way to screen for neural toxins, helping flag chemicals that ...

Gene mutation discovered in blood disorder

8 hours ago

An international team of scientists has identified a gene mutation that causes aplastic anemia, a serious blood disorder in which the bone marrow fails to produce normal amounts of blood cells. Studying a family in which ...

Airway muscle-on-a-chip mimics asthma

10 hours ago

The majority of drugs used to treat asthma today are the same ones that were used 50 years ago. New drugs are urgently needed to treat this chronic respiratory disease, which causes nearly 25 million people ...

User comments : 0