Navigation Links
Researchers discover human immune system has emergency backup plan

New research by scientists at the University of California, San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences reveals that the immune system has an effective backup plan to protect the body from infection when the "master regulator" of the body's innate immune system fails. The study appears in the December 19 online issue of the journal Nature Immunology.

The innate immune system defends the body against infections caused by bacteria and viruses, but also causes inflammation which, when uncontrolled, can contribute to chronic illnesses such as heart disease, arthritis, type 2 diabetes and cancer. A molecule known as nuclear factor kappa B (NF-κB) has been regarded as the "master regulator" of the body's innate immune response, receiving signals of injury or infection and activating genes for microbial killing and inflammation.

Led by Michael Karin, PhD, Distinguished Professor of Pharmacology, the UC San Diego team studied the immune function of laboratory mice in which genetic tools were used to block the pathway for NF-κB activation. While prevailing logic suggested these mice should be highly susceptible to bacterial infection, the researchers made the unexpected and counterintuitive discovery that NF-κB-deficient mice were able to clear bacteria that cause a skin infection even more quickly than normal mice.

"We discovered that loss of NF-κB caused mice to produce a potent immune-activating molecule known as interleukin-1 beta (IL-1β), which in turn stimulated their bone marrow to produce dramatically increased numbers of white blood cells known as neutrophils," said Karin. Neutrophils are the body's front-line defenders against infection, capable of swallowing and killing bacteria with a variety of natural antibiotic enzymes and proteases.

The new research demonstrates that the innate immune system deploys two effective strategies to deal with invasive bacterial infection, and that the IL-1β system provides an important safety net when NF-κB falls short.

"Having a backup system in place is critical given the diverse strategies that bacterial pathogens have evolved to avoid bacterial clearance," said Victor Nizet, MD, professor of pediatrics and pharmacy, whose laboratory conducted the infectious challenge experiments in the study. "A number of bacteria are known to suppress pathways required for NF-κB activation, so IL-1β signaling could help us recognize and respond to these threats."

While helpful in short-term defense against a severe bacterial infection, the dramatic increase in neutrophil counts seen in the NF-κB-deficient mice ultimately came at a cost. Over many weeks, these activated immune cells produced inflammation in multiple organs and led to the premature death of the animals. Long-term blockade of NF-κB signaling has been explored extensively by the biotechnology and pharmaceutical industry as a strategy for anti-inflammatory or anti-cancer therapy, perhaps unaware of the risks suggested by this new research.

"One might contemplate adding a second inhibitor of IL-1β signaling to protect against the over-exuberant neutrophil response," said Karin. "Unfortunately, loss of both the NF-κB pathway and the backup IL-1β pathway rendered the mice highly susceptible to invasive bacterial infection which they no longer cleared."

Altogether, the UC San Diego research sheds new light on the complex and elegant regulatory pathways required for a highly effective innate immune system. The scientists noted that future investigations must take into account these interrelationships in order to design novel drugs against inflammatory diseases that achieve their treatment goals while minimizing the risk of infection.


Contact: Scott LaFee
University of California - San Diego

Related biology news :

1. NC State researchers get to root of parasite genome
2. Researchers find animal with ability to survive climate change
3. Researchers find an essential gene for forming ears of corn
4. Researchers note differences between people and animals on calorie restriction
5. Researchers study acoustic communication in deep-sea fish
6. Researchers discover that growing up too fast may mean dying young in honey bees
7. Researchers study how pistachios may improve heart health
8. UI researchers find potentially toxic substance present in Chicago air
9. Researchers develop new self-training gene prediction program for fungi
10. Case Western Reserve University researchers track Chernobyl fallout
11. Childrens National researchers develop novel anti-tumor vaccine
Post Your Comments:
(Date:10/29/2015)... ANN ARBOR, Mich. , Oct. 29, 2015 ... with Eurofins Genomics for U.S. distribution of its ... DNA-seq kit and Rubicon,s new ThruPLEX Plasma-seq ... DNA to enable the preparation of NGS libraries ... in plasma for diagnostic and prognostic applications in ...
(Date:10/29/2015)... , Oct. 29, 2015 Today, ... a partnership with 2XU, a global leader in ... a smart hat with advanced bio-sensing technology. The ... athletes to monitor key biometrics to improve overall ... partnership, the two companies will bring together the most ...
(Date:10/27/2015)... Oct. 27, 2015 Synaptics Inc. (NASDAQ: SYNA ... that Google has adopted the Synaptics ® ClearPad ... to power its newest flagship smartphones, the Nexus 5X ... --> --> Synaptics ... provide strategic collaboration in the joint development of next ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... 25, 2015 Studies reveal the ... plaque and pave the way for more effective treatment for ...     --> --> ... health problems in cats, yet relatively little was understood about ... studies have been conducted by researchers from the WALTHAM Centre ...
(Date:11/25/2015)... , Nov. 25, 2015 Orexigen® Therapeutics, Inc. ... participate in a fireside chat discussion at the Piper ... York . The discussion is scheduled for Wednesday, ... .  A replay will be available for ... Stilwell  , Julie NormartVP, Corporate Communications and Business ...
(Date:11/24/2015)... , Nov. 24, 2015 Cepheid (NASDAQ: ... be speaking at the following conference, and invited investors ... York, NY      Tuesday, December 1, 2015 at ... York, NY      Tuesday, December 1, 2015 at ... Healthcare Conference, New York, NY ...
(Date:11/24/2015)... CITY , Nov. 24, 2015 /PRNewswire/ - Aeterna ... request of IIROC on behalf of the Toronto Stock ... news release there are no corporate developments that would ... --> --> About ... . --> Aeterna Zentaris is ...
Breaking Biology Technology: