Science Current Events | Science News | Brightsurf.com
 
Email a Friend Send to a friend
Printer Friendly Print Parasites that live inside cells use loophole to thwart immune system

Parasites that live inside cells use loophole to thwart immune system

November 04, 2008

A study from St. Jude scientists shows how microbes can block nitric oxide production-a chemical key to the immune system -- and offers hints for fighting bacteria

St. Jude Children's Research Hospital scientists have discovered a mechanism by which intracellular pathogens can shut down one of the body's key chemical weapons against them: nitric oxide. The researchers found that the microbes block nitric oxide production by subverting the biochemical machinery used by immune cells called macrophages to produce the chemical.




Macrophages are the battle tanks of the immune system, attacking and consuming bacteria and parasites, shredding them with enzymes and poisoning them with nitric oxide. However, some pathogens, such as those that cause tuberculosis and toxoplasmosis, have evolved to live and proliferate within macrophages themselves. To do so, these intracellular pathogens deploy an arsenal of weapons to avoid and counterattack macrophage's own weapons.

In their study that appears in the advance online publication of the journal Nature Immunology, St. Jude researchers focused on the role the microbes play in activating the macrophages to make an enzyme called arginase. The arginase enzyme occurs naturally in macrophages, but is normally only expressed under very specific circumstances, including when macrophages might make too much nitric oxide.

"Although the findings are basic, they suggest that it might be feasible to develop drugs to block such pathogens' biochemical subversion, restoring nitric oxide production and empowering macrophages to attack the invaders," said Peter Murray, Ph.D., an associate member of the St. Jude departments of Infectious Diseases and Immunology.

Previously other researchers had shown that pre-activating arginase in macrophages grown in the culture dishes can block nitric oxide production in macrophages by breaking down the chemical arginine, which the macrophages need to make nitric oxide. "However, no one had really explored the possibility that intracellular pathogens could directly exploit arginase-activation as a defense until now," said Murray, the paper's senior author.

To discover whether pathogens could be induced to mount such a defense in macrophages, the St. Jude team studied the arginase-inducing activity of the microorganisms that cause tuberculosis and toxoplasmosis, as well as a relative of tuberculosis, Mycobacterium bovis, that is used as a live vaccine.

Studies in macrophages in the culture dish and in mice demonstrated that these microbes did trigger arginase production and that this triggering suppressed nitric oxide production in macrophages. The researchers also traced the biochemical mechanism by which the organisms triggered arginase-finding that the microbes hijack the machinery by which the macrophages recognize invading pathogens.

Also working with mice, the researchers tested whether shutting down arginase might enhance the ability to battle tuberculosis. They found that mice genetically engineered to lack arginase only in their macrophages showed superior resistance to tuberculosis and toxoplasmosis.

"Our findings reveal that these pathogens have evolved to exploit a biological loophole in the immune system," Murray said. "This discovery offers two important insights. It reaffirms the notion that pathogens have an incredibly diverse way of manipulating their hosts. And it reveals a new pathway by which a pathogen can induce an enzyme that is normally not present in those macrophages and use the induction of that enzyme to its advantage."

Murray emphasized that the findings are basic, and that the researchers can only speculate about possible clinical implications at the moment. "However, we believe it could be possible to develop targeted drugs to specifically inhibit pathogens' ability to induce arginase in macrophages," he said. Such drugs might suppress such diseases as tuberculosis and toxoplasmosis by increasing the ability of macrophages to make nitric oxide. Researchers believe that the drugs could work in combination with existing treatments for tuberculosis and parasites-dealing the diseases a therapeutic one-two punch.

St. Jude Children's Research Hospital



Related Macrophages Current Events and Macrophages News Articles Macrophages Current Events and Macrophages News RSS Macrophages Current Events and Macrophages News RSS
New insight in the fight against the Leishmania parasite
Professor Albert Descoteaux's team at Centre INRS - Institut Armand-Frappier has gained a better understanding of how the Leishmania donovani parasite manages to outsmart the human immune system and proliferate with impunity, causing visceral leishmaniasis, a chronic infection that is potentially fatal if left untreated.

Sperm may play leading role in spreading HIV
Sperm, and not just the fluid it bathes in, can transmit HIV to macrophages, T cells, and dendritic cells (DCs), report a team led by Ana Ceballos at the University of Buenos Aires in Argentina.

Stanford study identifies cellular mechanism that causes lupuslike symptoms in mice
Macrophages, the scavenger cells of the body's immune system, are responsible for disposing of dying cells. Stanford University School of Medicine researchers have identified one pathway in this important process in mice that, if disrupted, causes a lupuslike autoimmune disease.

Major discovery opens door to leishmania treatment
Leishmania is a deadly parasitic disease that affects over 12 million people worldwide, with more than 2 million new cases reported every year.

Reactive oxygen in fruit flies acts as a cell signalling mechanism for immune response
For years, health conscious people have been taking antioxidants to reduce the levels of reactive oxygen in their blood and prevent the DNA damage done by free radicals, which are the result of oxidative stress. But could excessive use of antioxidants deplete our immune systems?

To regenerate muscle, cellular garbage men must become builders
For scientists at the European Molecular Biology Laboratory (EMBL) in Monterotondo, Italy, what seemed like a disappointing result turned out to be an important discovery.

Pitt study finds molecular link between insulin resistance and inflammation
An exploration of the molecular links between insulin resistance and inflammation may have revealed a novel target for diabetes treatment, say scientists at the John G. Rangos Sr. Research Center, Children's Hospital of Pittsburgh of UPMC.

Einstein researchers identify potential target for metastatic cancer
The deadliest part of the cancer process, metastasis, appears to rely on help from macrophages, potent immune system cells that usually defend vigorously against disease, researchers at Albert Einstein College of Medicine of Yeshiva University report.

Scientists open doors to diagnosis of emphysema
Chronic inflammatory lung diseases like chronic bronchitis and emphysema are a major global health problem, and the fourth leading cause of death and disability in developed countries, with smoking accounting for 90% of the risk for developing them.

Researchers capture bacterial infection on film
Whilst most studies of bacterial infection are done after the death of the infected organism, this system developed by scientists at the University of Bath and University of Exeter is the first to follow the progress of infection in real-time with living organisms.
More Macrophages Current Events and Macrophages News Articles
Macrophages and Dendritic Cells: Methods and Protocols (Methods in Molecular Biology)

Macrophages and Dendritic Cells: Methods and Protocols (Methods in Molecular Biology)
by Neil E. Reiner (Editor)

In light of the critical contributions of macrophages and dendritic cells to diverse inflammatory diseases and to immunity and host defense, state-of-the-art approaches to the investigation of their behavior are essential. In Macrophages and Dendritic Cells: Methods and Protocols, expert researchers contribute laboratory protocols involving these two vital cell types functioning at the junction of the innate and acquired immune systems. The volume delves first into isolation and cell culturing then continues with topics such as phagocytosis, genetic manipulation, macrophage activation, and lipid signaling. Written in the highly successful Methods in Molecular Biology™ series format, chapters include brief introductions to their respective subjects, lists of the necessary materials...

The Macrophage

The Macrophage
by Bernard Burke (Editor), Claire E. Lewis (Editor)

The field of macrophage research has grown enormously since publication of the first edition of this book. The Macrophage 2e provides a unique comprehensive review of the current scientific knowledge of the multifaceted role of this important and intriguiging cell in health and disease. In 16 chapters by experts in the field it covers the basic biology and diverse functions of macrophages in specific diseases and the complex of interactions between macrophages and other cells. Ranging from their role in the defense against pathogens, their role as hosts for pathogens (including HIV), their complex roles in diseases such as arthritis and cancer, and their potential for use in novel gene therapy approaches to disease treatment, the book gives an up to the minute account of active...

Source Naturals AHCC Active Hexose Correlated Compound 750mg, 60 capsules

Source Naturals AHCC Active Hexose Correlated Compound 750mg, 60 capsules
by Source Naturals

Dietary supplement. Active hexose correlated compound. Increases natural killer cell activity. AHCC (Active Hexose Correlated Compound) is a proprietary compound produced by cultivation and enzymatic modification of several species of mushroom mycelia, including shiitake, grown in rice bran extract. Considered a superfood supplement in Japan, AHCC has been researched extensively for its immune enhancement properties. According to human and animal research, AHCC may significantly increase Natural Killer (NK) cell activity. AHCC may also increase macrophage activity, enhance cytokine production, and support the healthy functioning of the liver as well as act as an antioxidant. (These statements have not been evaluated by the Food and Drug Administration. This product is not intended to...

  Macrophage the Toil and the Reap



Macrophage

Macrophage
Sun Project (Primary Contributor)



Lymph Nodules Node Sem Lymphocytes and Macrophages Photographic Poster Print, 16x12

Lymph Nodules Node Sem Lymphocytes and Macrophages Photographic Poster Print, 16x12
by AllPosters.com

AllPosters.com is the world's #1 seller of posters, prints, photographs, specialty products and framed art. We're dedicated to bringing our customers the best selection of high quality wall décor that is perfect for their home or office. Browse our catalog of over 300,000 items that include entertainment and specialty posters, decorative prints, and art reproductions. Whether you're looking for your favorite movie or music poster, a framed Monet reproduction, or a print of the Eiffel Tower you will find it at AllPosters.com. Visit our Amazon store today at www.amazon.com/allposters to find Special Offers and search by subject category or artist. AllPosters.com provides unmatched service with a 100% satisfaction guarantee. We ship internationally to over 80 countries. Decorate your...

Macrophages: A Practical Approach (Practical Approach Series)

Macrophages: A Practical Approach (Practical Approach Series)
by Donna M. Paulnock (Editor)

Univ. of Wisconsin. Provides data on the isolation, activation, and monitoring of diverse macrophage activities. Includes a variety of current techniques for the measurement of a board range of macrophage activities. Softcover, hardcover also available.

Teaching About Immunity Kit

Teaching About Immunity Kit
by American Educational Products

This kit clearly displays the interrelated workings of the Immunity System. Attack an invading anigen with a phagocyte or monbyte. Produce macrophages. T-Cells, B-Cells, Plasma Cells, and antibodies. Clone T and B cells to produce Helper, Killer, Memory and Suppression cells. Demonstrate the operation of AIDS, Cancer, Vaccines, Allergies, Autoimmune reactions and more right on the board. Students can readily participate in the "hands on" activities. The Plastick pieces will not break, chip, tear, peel or wear out! Comes complete with a 30" X 40" Demonstration Board, mounting legs, and Teacher's Guide with detailed lesson plans plus reproducible student worksheets.

  Lentiviruses and Macrophages: Molecular and Cellular Interactions
by Moira Desport (Editor)



Planetary Herbals Full Spectrum Astragalus Extract, 500 mg, Tablets , 120 tablets (Pack of 2)

Planetary Herbals Full Spectrum Astragalus Extract, 500 mg, Tablets , 120 tablets (Pack of 2)
by Planetary Formulas

Herbal supplement. Botanical immune support. Astragalus is one of the primary immune tonifiers of Chinese herbalism. Full Spectrum Astragalus Extract combines a standardized astragalus extract with whole, high grade astragalus root, to ensure the presence

© 2009 BrightSurf.com