Navigation Links
Elderly might not benefit from TB vaccines in development
Date:9/20/2010

COLUMBUS, Ohio Elderly people might not benefit from some of the tuberculosis vaccines currently in development, recent research suggests.

Some vaccines under study are designed to activate a specific molecule that is an early participant in the immune response against TB in young people. But a recent Ohio State University study suggests that in older people, this molecule remains relatively inactive, even in the face of TB infection.

The animal research suggests that the presence of this molecule, called a toll-like receptor, is not required in an old mouse to generate an immune response to Mycobacterium tuberculosis, the pathogen that causes TB infection. The immune response in young mice without the receptor, however, is not robust enough to adequately fight TB infection.

So while young people would stand to benefit from a vaccine that boosts this molecule's function, it appears a new direction in vaccine research is needed to ensure that the elderly also receive protection against the disease, researchers say.

One caveat, says Joanne Turner, associate professor of internal medicine at Ohio State and lead author of the paper, is that this finding occurred in mice that are completely lacking the receptor in question.

"If old mice have this receptor on the surface of their cells, it probably functions, but not as well as it should, and not as well as it does when mice are younger," Turner said. "When we take it away, something else works on its behalf. Our next step will be to find which receptor is responsible in old mice for sending the immune response signals, because that should be the focus of a vaccine for the elderly."

The study is published in a recent issue of the journal Mechanisms of Aging and Development.

About 2 billion people worldwide are thought to be infected with Mycobacterium tuberculosis. People can harbor the bacterium without symptoms for decades, but an estimated one in 10 will develop active disease characterized by a chronic cough and chest pain. The elderly are considered highly susceptible to both reactivation of latent infection and newly acquired infections, especially in long-term care facilities. Many older patients cannot tolerate the months-long antibiotic regimen required to treat active TB.

Despite that higher infection susceptibility, researchers still do not know exactly what happens during aging that either weakens the immune response or otherwise reduces elderly people's ability to fight infection.

Turner and colleagues focused this work on the molecule known as TLR-2, or toll-like receptor-2. It is among the receptors located on the surface of macrophages, which are the first cells in the lungs to see Mycobacterium tuberculosis at the point of infection.

The job of TLR-2 and at least two other known receptors is to recognize distinctive characteristics of dangerous pathogens and then send out signals to activate other players in the immune system.

Previous research has shown that TLR-2 has a prominent role in macrophages' ability to see and absorb the TB pathogen in young mice and humans hence, vaccines that boost TLR-2 would be expected to reduce the chances that the infection can get past this first line of the body's defense.

But in this more recent study, Turner and colleagues found that the macrophages in old mice respond as they are supposed to when Mycobacterium tuberculosis invades the lungs but they do so without the help of the TLR-2 receptor.

First, the researchers showed that the immune function of old and young mice were comparable in response to infection. The receptors on cell surfaces were present at similar levels and those cells made the same proteins needed for infection control.

To test the TLR-2 function in particular, the researchers observed cells in mice genetically modified to be lacking this molecule. They aged some of these mice for 18 months equivalent to about 65 in human years and compared these old mice to young mice with the same genetic modification.

"This time, we showed there was a difference. The immune system in the old mice worked, but it didn't use the TLR-2 receptor," said Turner, also an investigator in Ohio State's Center for Microbial Interface Biology. "Young mice without TLR-2 lost 80 percent of their immune response to Mycobacterium tuberculosis, but old mice didn't lose any response at all."

From there, the researchers blocked two other receptors, one associated with TB and another connected to recognition of other bacteria. Blocking them alone or in combination did not influence the way the immune systems in old mice recognized Mycobacterium tuberculosis. There are 13 known toll-like receptors on macrophages, but the researchers initially worked with TLR-4 and TLR-9 because their functions are known and can be blocked.

"We think the cells in the old mice might be using multiple TLRs to send their signals," Turner said. "We don't know yet whether this receptor interaction changes how the bacteria are processed within the cell. It might be that the bacteria go to a different location in the cells of old mice, to a place where the immune system can't respond so well which might be why old people are more susceptible to TB infection."

Turner plans to investigate some or all of those 10 other toll-like receptors to determine their roles in helping lung cells in old mice identify and fight Mycobacterium tuberculosis.


'/>"/>

Contact: Joanne Turner
joanne.turner@osumc.edu
614-292-6724
Ohio State University
Source:Eurekalert

Related medicine news :

1. European partnership funds research toward robot aides for the elderly
2. Institute for Aging Research study finds indoor and outdoor fall are different for the elderly
3. Surgery to repair torn shoulder muscles in the elderly can reduce pain and improve function
4. Childhood abuse, adversity may shorten life, weaken immune response among the elderly
5. New links between cholesterol and depression in the elderly
6. Childhood malnutrition could weaken brain function in elderly
7. Low vitamin D linked to the metabolic syndrome in elderly people
8. Higher testosterone may raise risk of heart disease in elderly men
9. Tray bleaching may improve oral health of elderly, special-needs patients
10. Institute for Aging Research study says going barefoot in home may contribute to elderly falls
11. Study finds that caring for an elderly, sick spouse sometimes has positive elements
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/8/2016)... (PRWEB) , ... December 08, 2016 , ... ... accreditation with distinction by the Undersea and Hyperbaric Medical Society (UHMS), the leading ... advanced care and patient safety. Only a few hospitals and facilities have earned ...
(Date:12/8/2016)... ... 08, 2016 , ... Mirixa Corporation , a leading ... pharmacist-delivered patient care services, has announced the promotions of Karen Litsinger to senior ... of sales. , Litsinger joined Mirixa in 2008 after serving as a ...
(Date:12/8/2016)... ... December 08, 2016 , ... SunView ... customers and employees that are both engaging and easy to use. Coming off ... the software company revealed today its plans to roll out new AI-powered self-service ...
(Date:12/8/2016)... , ... December 08, 2016 , ... California Senate Bill ... payments per workers’ compensation claim in 2013 and 2014, according to CompScope™ Medical ... Institute (WCRI) . , According to the study, medical payments per claim in California ...
(Date:12/8/2016)... ... December 08, 2016 , ... The Dianne Michael Insurance ... in Hamilton County, is embarking on a charity drive with the aim of ... homes for orphaned or neglected senior dogs in the Cincinnati region, and LuvFurMutts ...
Breaking Medicine News(10 mins):
(Date:12/9/2016)... Dec. 9, 2016  Forge Therapeutics, Inc. today ... Stock Exchange: EVT, TecDAX, ISIN: DE0005664809) to advance ... the treatment of bacterial infections including those caused ... as an attractive antibacterial target for more than ... suitable chemical starting points has hampered its progress. ...
(Date:12/8/2016)... , Dec. 8, 2016 Australia Ophthalmic ... new report, "Australia Ophthalmic Lasers Market Outlook to 2022", ... market. The report provides value, in millions of US ... market segements - Excimer Lasers, Femtosecond Lasers and YAG ... distribution shares data for each of these market segements, ...
(Date:12/8/2016)... Dec. 8, 2016 KEY FINDINGS ... Patient warming ... of blood during surgeries, lowering the risks of neurological disorders ... of SSIs. The patient warming systems can be segmented into ... benefits in turn reduce the stay at hospitals thus, lowering ...
Breaking Medicine Technology: