Wolf in sheep's clothing: Uncovering how deadly bacteria trick the immune system

Friday, March 1, 2013

An outbreak of tuberculosis in the skid row area of downtown Los Angeles may have exposed up to 4,500 individuals to the bacterium that causes the deadly disease and has left federal officials scrambling to intervene.

The outbreak is occurring during winter, when homeless individuals are driven to crowded shelters, when influenza is peaking and when people's vitamin D levels, typically boosted by sunlight exposure, are low. A new UCLA study offers critical insight into how various bacteria may manipulate such factors to their advantage.

In a study published online Feb. 28 in the journal Science, UCLA researchers demonstrate that certain cunning bacteria ? including the type that causes tuberculosis ? can pretend to be viruses when infecting humans, allowing them to hijack the body's immune response so that they can hide out, unhindered, inside our cells. The findings may also help explain how viral infections like the flu make us more susceptible to subsequent bacterial infections such as pneumonia.

The study is particularly relevant to tuberculosis, which kills 1.4 million people worldwide each year. In the case of the recent Los Angeles outbreak, the findings could provide clues as to how the flu and a lack of vitamin D may have given the tuberculosis bacterium an edge.

"With 8.7 million in the world falling ill with tuberculosis each year, a better understanding of how these bacteria avoid our immune system could lead to new ways to fight them and to better, more targeted treatments," said senior author Dr. Robert L. Modlin, chief of dermatology at the David Geffen School of Medicine at UCLA and a professor of microbiology, immunology and molecular genetics in the UCLA Division of Life Sciences.

The protection our immune system provides against bacteria-based diseases and infections depends on the critical response of T cells ? white blood cells that play a central role in fighting infections ? and in particular on the release of a protein called interferon-gamma. Interferon-gamma utilizes the vitamin D hormone to alert and activate cells to destroy invading bacteria.

The research team found that bacteria can pretend to be viruses, triggering the immune system to launch an attack with a different protein, called interferon-beta, which is designed to fight viruses, not bacteria. Not only is interferon-beta ineffective against bacteria, but it can also block the action of interferon-gamma, to the advantage of bacteria. Further, if a real virus were to infect the body, triggering interferon-beta, it would divert the attention of the immune response, preventing an attack on the bacterial invader. The researchers say this may explain why the flu can lead to a more serious bacterial-based infection like pneumonia.

"Like a wolf in sheep's clothing, the bacteria can fool the immune system into launching an attack against the wrong type of infection, thus weakening the response against the bacteria," said first author Rosane M. B. Teles, a researcher in the dermatology division at the Geffen School of Medicine.

For the study, the team examined the mechanisms by which the virus-fighting interferon-beta protein suppresses the interferon-gamma defense response to bacterial infections, tricking the immune system into making the wrong defense choices.

The researchers studied leprosy as a model and then applied what they learned to understand tuberculosis, given that leprosy and tuberculosis are caused by related bacteria. Modlin noted that leprosy is an outstanding model for studying immune mechanisms in host defense since it presents as a clinical spectrum that correlates with the level and type of immune response of the pathogen.

The scientists first compared the genetic expression of the virus-fighting interferon-beta protein and the bacteria-fighting interferon-gamma protein in skin lesions from leprosy patients. They found that interferon-gamma was expressed in patients with the milder form of the disease and that interferon-beta was significantly increased in those with the more serious, progressive form of leprosy.

The researchers then compared the genes triggered by interferon-beta in these leprosy skin lesions with those found by two other groups of investigators in the blood of tuberculosis patients. Remarkably, there was a significant overlap. The interferon-beta genes were more frequent in both the skin lesions of leprosy patients with extensive disease and the blood of tuberculosis patients with more severe disease.

"We found this common interferon-beta gene pattern correlated with the greater extent of disease in both leprosy and tuberculosis, which are two very distinct diseases," Teles said.

Previous work by the UCLA team demonstrated that the interferon-gamma defense pathway relies on a specific mechanism involving vitamin D, a natural hormone that plays an essential role in the body's fight against infections. The current study found that interferon-beta suppressed elements involved in the interferon-gamma?triggered vitamin D pathway, preventing the immune system from killing the bacteria.

"The study raises the possibility that a decrease or increase of one of these two interferon proteins could shift the balance from mild to more serious disease," Modlin said. "We may find that therapeutic interventions to block or enhance specific interferon responses may be an effective strategy to alter the balance in favor of protection against bacterial diseases."

The new findings may indicate why, in winter, Los Angeles skid row residents are at an added disadvantage in dealing with tuberculosis ? for at least three reasons. First, because of colder weather at night, indigent homeless people tend to stay in shelters, where they live in close proximity with others, facilitating the spread of the infection. Second, due to the seasonal rise in influenza, the body's immune system could be diverted by the flu virus to produce interferon-beta, blocking an effective immune response to the tuberculosis bacteria. And finally, the drop in vitamin D levels associated with a decrease in exposure to sunlight during the winter months could diminish the ability of individuals' immune systems to kill the tuberculosis bacteria.

"With TB on the rise, this scenario could play out not only in cities in the United States but all over the world," Modlin said. "We hope that our findings may provide insight into harnessing new methods to combat TB and other bacterial infections as well."

Modlin noted that 8.7 million become ill with tuberculosis each year, and 1.4 million die from the disease. He added that an increase or decrease in one of the two interferon proteins could help explain why some people may be more resilient against or susceptible to the infection or have a more serious course of the disease.

The next step, according to Teles, is to further understand the mechanisms that bacterial pathogens use to activate interferon-beta and how bacteria can manipulate the immune system to block the potent interferon-gamma host antimicrobial responses in human infections.

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University of California - Los Angeles Health Sciences: http://www.uclahealth.org/

Thanks to University of California - Los Angeles Health Sciences for this article.

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Source: http://www.labspaces.net/127087/Wolf_in_sheep_s_clothing__Uncovering_how_deadly_bacteria_trick_the_immune_system_

Man missing after sinkhole appears under Fla. home

WFLA

A sinkhole opened up inside a Brandon, Fla., house Thursday night, trapping a man inside.

By Ian Johnston, Staff Writer, NBC News

A man is missing after a giant sinkhole appeared during the night under his house near Tampa, Florida, a fire department spokeswoman said Friday.

Jessica Damico, a spokeswoman for Hillsborough County Fire Department, said first responders had been unable to make contact with the 34-year-old man, who was presumed dead. She stressed his death had not been confirmed.

Damico said firefighters were called to the house in Brandon just after 11 p.m. Thursday and said more equipment was being brought to the scene.

She said the scene was unstable and that rescuers had been unable to get close because of the danger.

Damico said that the sinkhole was 30 feet across at the surface, but said engineers had estimated that below the surface it could be 100 feet wide, and 50 feet deep.

A deputy sheriff who was first on the scene pulled out the missing man?s brother from the collapsing house, NBC station WFLA.com reported.

"He basically just reacted and did what he had to do to get that person out," Lt. Donald Morris with Hillsborough County Sheriff?s Office told the station.

Dexter Barge with Hillsborough County?s Code Enforcement was also on the scene.

"It's the only one we've seen that opened up in this manner there is no evidence of the structure cracking or anything like that on the outside of the house,? he told WFLA.

County officials said the house was considered too unstable to continue rescue efforts on Friday, according to the Associated Press.

Source: http://usnews.nbcnews.com/_news/2013/03/01/17145165-man-missing-brother-rescued-after-giant-sinkhole-appears-under-house-near-tampa-florida?lite

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Many Venezuelans believe in Chavez recovery

CARACAS, Venezuela (AP) ? Venezuela's vice president said Thursday that Hugo Chavez is still fighting for his life, yet a recent poll says three in five Venezuelans believe their president will return to power.

Nicolas Maduro, Chavez's self-appointed successor, said on television that his boss "is battling there for his health, for his life, and we're accompanying him."

The vice president had characterized Chavez's condition similarly on Dec. 20, saying the president "is fighting a great battle ... for his life, for his health."

Chavez hasn't spoken or been seen since before his fourth operation in Cuba on Dec. 11 for an unspecified cancer in the pelvic area.

The government says he has been breathing with the help of a tracheal tube after surviving a serious respiratory infection. It says Chavez returned on Feb. 18 and is at a military hospital in Caracas for continued treatment for "respiratory insufficiency."

Despite speculation by doctors not involved in Chavez's treatment that it is most likely palliative, designed only to make him more comfortable in his remaining days, many Venezuelans apparently believe ? or want to believe ? he is on the mend.

"The president's prolonged absence and his critical situation have not been converted into massive pessimism about his return," respected pollster Luis Vicente Leon tweeted Thursday.

He said nearly 58 percent of Venezuelans believe Chavez will recover while about 30 percent believe he will not return to power and 12.5 percent say they don't know what will happen. One percent, meanwhile, believe Chavez was never sick.

Leon, chief of the Datanalisis polling firm, told The Associated Press that the Feb. 11 poll of 1,198 people had an error margin of three percentage points.

He said he thought the poll reflected people's desire not to believe the worst about someone who is dear to them, just as people resist accepting that a close relative might be dying.

Leon also said he thought reports of government officials holding hours-long meetings with Chavez had contributed to the belief of many Venezuelans that Chavez will return.

"The government has sent permanent messages that President Chavez will return, that he meets with the vice president for five hours," Leon noted.

He said people don't necessarily believe that, however, as the poll found 44 percent think the government has not been transparent in discussing the Chavez's health.

In his televised remarks, Maduro called for Venezuelans to keep praying for Chavez and remain loyal to the committed socialist who has been their president for more than 19 years.

"Do you know why Comandante Chavez neglected his health and has been battling (cancer) for nearly two years?" he said. "Because he completely surrendered body and soul and forgot all his obligations to himself in order to give himself to the homeland."

Chavez, 58, himself has previously acknowledged that he was neglecting his health in recent years, often staying up late and consuming cup after cup of coffee to remain alert.

The president has undergone surgeries, chemotherapy and radiation treatments since June 2011, when he first announced his cancer diagnosis. He hasn't specified the type of cancer or the exact location in his pelvic region where his tumors have been removed.

On Feb. 15, the government released four photographs of Chavez lying in a bed in Cuba with his two daughters by his side. They were the only images of him published since early December.

Re-elected in October, Chavez was scheduled to have been sworn in on Jan. 10. But the Supreme Court said the swearing-in could be delayed.

___

Frank Bajak on Twitter: http://twitter.com/fbajak

Source: http://news.yahoo.com/many-venezuelans-believe-chavez-recovery-224906127.html

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The ever-expanding smartphone screen: how supersized became everyday

It used to be that any smartphone screen beyond three inches was considered big -- and it was, for an audience still weaning itself off of flip phones and PDAs. Flash-forward several years, however, and we're to the point where many won't even consider less than a 4-inch screen, and the once-unfathomable 5-inch display is quickly becoming the de facto standard for high-end models. It's clear that many of us like our phones supersized, Zack Morris style. But when the 6.1-inch Ascend Mate is a reality, and Mobile World Congress or future events may push the boundaries even further, there's still a worry that the focus on successively bigger displays might have gone too far. Have we pushed too hard for more glass? Or are we witnessing a wholesale shift away from the smartphone as we once knew it? There's truth to both sides. Follow along as we look at how smartphones have swelled over time, and how we're learning to love (or cope with) their dimensions.

Filed under: Cellphones, Mobile, Apple, Samsung, Sony, HTC, Nokia, Google, LG, Blackberry

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Source: http://feeds.engadget.com/~r/weblogsinc/engadget/~3/PecZz_-91tA/

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