MOSCOW (AP) ? Russia voiced strong skepticism Saturday about the U.S. autopsy on a 3-year-old adopted Russian boy in Texas and demanded further investigation as thousands rallied in Moscow to support the Kremlin ban on U.S. adoptions of Russian children.
Max Shatto's death in January, ruled accidental, came a month after Moscow passed a ban on international adoptions in retaliation for a new U.S. law targeting alleged Russian human rights violators. Russian officials have pointed at Max's case to defend the ban, which has drawn strong public criticism.
The boy, born Maxim Kuzmin, died Jan. 21 after his adopted mother, Laura Shatto, told authorities she found him unresponsive outside their home where he had been playing with his younger brother.
Ector County Sheriff Mark Donaldson and District Attorney Bobby Bland said Friday that four doctors reviewed the autopsy report and agreed that the boy's death was not intentional. Preliminary autopsy results had indicated Max had bruises on several parts of his body, but Bland said Friday that those bruises appeared to be self-inflicted. He also said no drugs were found in Max's system.
Foreign Ministry rights envoy Konstantin Dolgov said Saturday that Moscow "proceeds from the understanding that these are the preliminary results of the investigation" and urged U.S. authorities to produce autopsy documents and the boy's Russian passport.
The Investigative Committee, Russia's top investigative agency, has opened its own probe into the case. It said has sent a formal request to the U.S. to provide the autopsy and other related documents. The committee's spokesman, Vladimir Markin, said it also has urged U.S. authorities to allow Russian investigators take part in the U.S. probe.
Children rights ombudsman Pavel Astakhov, who initially claimed that the boy had been "murdered" by his adoptive parents, tweeted that Russia should "demand convincing proof."
Pro-Kremlin groups rallied in central Moscow to back the ban on U.S. adoptions of Russian children and call for more adoptions by Russian parents. Protesters held signs with pictures of adopted Russian children who died in the U.S. in recent years and wore ribbons in the colors of the Russian flag with slogans demanding Max's half brother Kirill be returned to Russia.
"Today people are telling us that Maxim supposedly maimed himself to death with a blunt instrument and damaged his own internal organs. That's a slap in the face of our country and our people," Irina Bergset, one of the march's organizers, said in a speech at the rally.
Olga Batalina, a lawmaker from the Kremlin-backed United Russia party who reportedly authored the adoption ban, said Saturday that Russia should work towards liquidating orphans as a class by focusing on state-sponsored "basic moral values."
Organizers claimed upwards of 20,000 attended, though police estimated numbers at 12,000. Two people were arrested. Approximately 25,000 attended a protest against the U.S. adoption ban in January.
The atmosphere at Saturday's march was festive and rather bizarre. Marchers included large groups of old people in fur coats, members of obscure esoteric communist parties, and organizations that had no apparent link to the march, including the Gardener's Union and a group for victims of the 1986 Chernobyl nuclear disaster in Ukraine. Organizers herded people into columns and handed out balloons as eerie pop music sung by children wafted over loudspeakers.
"I came here because Americans beat our children they adopt," Ivan Levin, a participant, said. "Ideally, that shouldn't happen."
A significant number of demonstrators had been bused in from as far as hundreds of miles away from Moscow, a common tactic to boost numbers at pro-Kremlin rallies. In the days leading up to the march, classified ads and letters on United Russia stationery appeared online offering people money to attend or demanding that business owners and university directors bring 50 people.
Organizers vehemently denied that anyone had been paid or coerced to attend. The independent RBK news agency, however, posted photos on Twitter of what it said were marchers being paid after the march ended.
President Vladimir Putin's spokesman, Dmitry Peskov, said on independent Rain TV Saturday that the rally demonstrated that "this problem has been very painful and sensitive for our people." He said that Russian diplomats had taken action to return the boy, but acknowledged that it would be difficult to achieve because the adoption process was in accordance with Russian law.
Last month, Russia's state-controlled Rossiya TV channel aired a talk show with the boy's biological mother, Yulia Kuzmina, who lost parental custody of Max and half brother Kirill Kuzmin over negligence and serious drinking problems. Kuzmina said during the show that she gave up drinking, had found a job and pledged to fight to regain custody of Kirill. But right after the show, Kuzmina and her boyfriend, who were traveling back from Moscow to their hometown, were taken off the train by police after a drunken brawl.
___
AP writers Vladimir Isachenkov and Laura Mills contributed to this report.
Feb. 27, 2013 ? A study published today in the journal Nature reports that a viral predator of the cholera bacteria has stolen the functional immune system of bacteria and is using it against its bacterial host. The study provides the first evidence that this type of virus, the bacteriophage ("phage" for short), can acquire a wholly functional and adaptive immune system.
The phage used the stolen immune system to disable -- and thus overcome -- the cholera bacteria's defense system against phages. Therefore, the phage can kill the cholera bacteria and multiply to produce more phage offspring, which can then kill more cholera bacteria. The study has dramatic implications for phage therapy, which is the use of phages to treat bacterial diseases. Developing phage therapy is particularly important because some bacteria, called superbugs, are resistant to most or all current antibiotics.
Until now, scientists thought phages existed only as primitive particles of DNA or RNA and therefore lacked the sophistication of an adaptive immune system, which is a system that can respond rapidly to a nearly infinite variety of new challenges. Phages are viruses that prey exclusively on bacteria and each phage is parasitically mated to a specific type of bacteria. This study focused on a phage that attacks Vibrio cholerae, the bacterium responsible for cholera epidemics in humans.
Howard Hughes Medical Institute investigator Andrew Camilli, Ph.D., of Tufts University School of Medicine led the research team responsible for the surprising discovery.
First author Kimberley D. Seed, Ph.D., a postdoctoral fellow in Camilli's lab, was analyzing DNA sequences of phages taken from stool samples from patients with cholera in Bangladesh when she identified genes for a functional immune system previously found only in some bacteria (and most Archaea, a separate domain of single-celled microorganisms).
To verify the findings, the researchers used phage lacking the adaptive immune system to infect a new strain of cholera bacteria that is naturally resistant to the phage. The phage were unable to adapt to and kill the cholera strain. They next infected the same strain of cholera bacteria with phage harboring the immune system, and observed that the phage rapidly adapted and thus gained the ability to kill the cholera bacteria. This work demonstrates that the immune system harbored by the phage is fully functional and adaptive.
"Virtually all bacteria can be infected by phages. About half of the world's known bacteria have this adaptive immune system, called CRISPR/Cas, which is used primarily to provide immunity against phages. Although this immune system was commandeered by the phage, its origin remains unknown because the cholera bacterium itself currently lacks this system. What is really remarkable is that the immune system is being used by the phage to adapt to and overcome the defense systems of the cholera bacteria. Finding a CRISPR/Cas system in a phage shows that there is gene flow between the phage and bacteria even for something as large and complex as the genes for an adaptive immune system," said Seed.
"The study lends credence to the controversial idea that viruses are living creatures, and bolsters the possibility of using phage therapy to treat bacterial infections, especially those that are resistant to antibiotic treatment," said Camilli, professor of Molecular Biology & Microbiology at Tufts University School of Medicine and member of the Molecular Microbiology program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts University.
Camilli's previous research established that phages are highly prevalent in stool samples from patients with cholera, implying that phage therapy is happening naturally and could be made more effective. In addition, a study published by Camilli in 2008 determined that phage therapy works in a mouse model of cholera intestinal infection.
The team is currently working on a study to understand precisely how the phage immune system disables the defense systems of the cholera bacteria. This new knowledge will be important for understanding whether the phage's immune system could overcome newly acquired or evolved phage defense systems of the cholera bacteria, and thus has implications for designing an effective and stable phage therapy to combat cholera.
Additional authors are David W. Lazinski, Ph.D., senior research associate in the Camilli lab at Tufts University School of Medicine, and Stephen B. Calderwood, M.D., Morton N. Swartz, M.D. academy professor of medicine at Harvard Medical School, and chief, division of infectious disease and vice-chair, department of medicine at Massachusetts General Hospital.
Research reported in this publication was supported by the National Institute of Allergies and Infectious Diseases of the National Institutes of Health under award numbers R01AI55058, R01AI045746, and R01AI058935.
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Journal Reference:
Kimberley D. Seed, David W. Lazinski, Stephen B. Calderwood, Andrew Camilli. A bacteriophage encodes its own CRISPR/Cas adaptive response to evade host innate immunity. Nature, 2013; 494 (7438): 489 DOI: 10.1038/nature11927
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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
She suffers from a rare genetic metabolic disorder called cystinosis, which prevents her from sweating. She lives in South Carolina, and can't stay in 80-degree weather for longer than 20 minutes, so during the summer she used to stay cooped up inside, her mother, Katie Larimore, told ABCNews.com.
Last summer her family built a swimming pool in their backyard.
"It was her first real, live outside summer," her mother said. "She just stayed in the water for three months."
Sarah is one of at least 25 million Americans who suffer from rare conditions, according to the National Institutes of Health, which recognizes today as Rare Disease Day. The last day of February has been promoted since 2009 by the National Organization for Rare Disorders (NORD) to increase awareness about the common needs of people with illnesses that not many others have.
People with a rare illness -- defined as affecting fewer than 2,000 people -- share common challenges: They have trouble getting an accurate diagnosis, finding treatment, and convincing insurance companies to pay for care, said Mary Dunkle, NORD spokeswoman.
"Even though each disease is different, the challenges of living with a disease that's rare is pretty consistent," she said.
Of the 6,000 to 7,000 rare diseases recorded in the U.S., treatment options exist for only a few hundred of them, Dunkle said. Treatment is more widely available than it was 30 years ago when NORD was founded, but there's a long way to go, a spokeswoman said.
Federal aid for people with rare illnesses is precarious, and it's often tough to persuade a pharmaceutical company to invest in treatment for a rare disease when there isn't a big payoff, Dunkle said.
Sarah, who loves reading and fashion as well as swimming, shares her diagnosis with about 500 Americans, according to the Cystinosis Research Network. A genetic metabolic disorder, cystinosis causes an amino acid, cystine, to accumulate in every cell of the body, damaging organs and blood cells. An estimated 2,000 people suffer from the illness worldwide.
Her daily regimen is grueling and embarrassing.
Sarah has to take 33 pills daily, a number that will increase to about 80 by the time she's a teenager, her mother said. Cystagon, a medication she takes six times a day, including in the middle of the night, makes her breath stink.
Every hour she has to apply eyedrops to prevent blindness. Seven times a day, she eats through a feeding tube, which causes a bump under her shirt. She has to get a daily injection of growth hormone.
Why she can't sweat is a "one of those mysteries of cystinosis," her mother said. If Sarah stays in the heat too long her cheeks turn red, her body temperature rises and she gets very faint.
Her mother visited Sarah's class to talk about her daughter's fragile condition.
"First-graders can be brutal," Katie Larimore said. But after learning about their classmate's condition, "they started talking about every uncle and cousin they had with an ingrown toenail. They felt empowered and embraced Sarah," she said.
Sarah will need a kidney transplant by the time she's about 15. But she can be considered one of the lucky ones. Children diagnosed years earlier than Sarah died by the time they were 15, he said. Now diagnosis is faster, her parents said.
A company is expected to get FDA approval for a new drug in coming months that could replace Cystagon. It would last for 12 hours instead of six, her parents said.
"Our kid would get to sleep all night. We would get to sleep all night," Katie Larimore said.
Larimore and her husband, Jeff, started noticing problems when Sarah was a baby. She was the youngest of their four children. By the time she was a year old she wasn't growing and needed to drink two gallons of water a day, her mother said.
"Being she was my fourth, I knew something was wrong," Katie Larimore said. "Sarah was very, very tiny at this point because she had stopped growing. I went from doctor to doctor until I found one that believed me."
Sarah's parents say they lucked out. They found a doctor who was treating another child in South Carolina for cystinosis. Soon Sarah was diagnosed. Only two labs in the country can test for the disease, her mother said.
"It was confirmed she had cystinosis and it was going to be a battle," she said. "But we had a name for it we knew what we were battling."
At their first national meeting for parents of children with the condition, eerily, the children of the genetic disorder looked like siblings, Katie Larimore said.
"They all kind of look alike. It's kind of scary," she said. "I thought we were going to pass out."
Last month the Larimores traveled with eight other families with children who have cystinosis to the Capitol to meet with legislative aides of 35 members of Congress. As the March 1 sequester budget cuts loomed, they argued in favor of keeping funding for programs designed to help people with rare illnesses, they said.
Those include the Orphan Drug Act of 1983, which gives pharmaceutical companies tax incentives and other help to research rare illnesses.
A Medicare policy known as TEFRA, or the Tax Equity and Fiscal Responsibility Act, allows middle-class families in 26 states to get federal dollars to help pay for care costs involved helping children with disabilities and serious illnesses. Each month the Larimores spend about $5,000 on medication, doctors' visits and supplies, most of which is currently covered by insurance, they said.
Finally the Larimores asked Congress to not slash funding to the National Institute of Health, which performs research on rare diseases.
"Right now we're coming down to the wire," Katie Larimore said. "As a mom, we'll fight for our kids. There's a lot of us out there who need that kind of help."
Subway co-founder Fred Deluca went on CNBC's Squawk on the Street and?ripped existing government regulations and the current business environment.
In fact, he said that Subway wouldn't exist if he founded it today.
"It's continuously gotten worse because there's more and more regulations and it's tough for people to get into business, especially a small business," said Deluca.
"I'll tell you, if i started Subway today, Subway would not exist," he continued. "Because I had an easy time of it in the 60s when I started and I just see a continuous increase in regulations."
Deluca cited Obamacare as?"the biggest concern of our franchisees."
"They don't know what to expect," he said. "It's causing a lot of concern, but that too will be passed on to the consumer."
Deluca's also worried about payroll taxes pressuring consumers. He said that it's "causing sales declines."
"I think this is on the permanent side," said Deluca. "But I think business will adjust to it."
DES MOINES, Iowa (AP) ? Iowa Congressman Tom Latham, who had been considered the establishment Republican choice for the U.S. Senate seat being vacated next year by retiring Democrat Tom Harkin, announced Wednesday that he won't seek the job.
Latham, a 10-term Republican from Clive, said in a statement that he could not "in good conscience launch a two-year statewide campaign that will detract from the commitment" to the new district he was elected to in November.
He faced considerable pressure to run from throughout the Iowa Republican establishment, including Iowa Gov. Terry Branstad. Latham, a soft-spoken former businessman, had represented more than half of Iowa's counties during nearly 20 years in Congress and was considered a good fundraising match for Democratic Rep. Bruce Braley.
Attention now turns to U.S. Rep. Steve King, an outspoken conservative who has said he is weighing a Senate bid but was not expected to challenge Latham in a primary. King said Wednesday in a statement: "It is too big a decision to be rushed."
King gave no timeline for a decision. "A potential Senate race remains an analytic decision first and then one that requires deep conviction," he said.
Democrats would have been expected to hold the seat before Harkin, 73, opted last month not to seek a sixth term. Republicans, who need to gain six seats in 2014 to win the Senate majority, immediately claimed to have a real shot at the seat.
But in the month since Harkin made his announcement, Democrats have coalesced around Braley, a four-term congressman from Waterloo. He is the only Democrat to announce his candidacy for the seat.
Trying to foster an organized process for Republicans, Iowa Gov. Terry Branstad had urged Latham this month during a private meeting at the governor's mansion in Des Moines to seek the nomination. Branstad, who also met with King privately, said he urged King to develop more of a statewide network and consider running in 2016, should Republican Sen. Charles Grassley decide against running for a sixth term.
A national group started by former George W. Bush adviser Karl Rove had identified King as a potential target of attack ads in its mission to field candidates more acceptable to general election audiences after GOP Senate candidates lost in races seen as within their reach in 2010 and 2012.
Branstad, who is expected to seek re-election next year, hopes to field a strong GOP ticket and avoid a potentially nasty Senate primary that could dishearten portions of the GOP coalition.
He also is urging Lt. Gov. Kim Reynolds, a loyal Branstad protege, to consider seeking the GOP Senate nomination.
"I know the respect and support she has throughout Iowa," Branstad said in a statement provided to The Associated Press. "I have been greatly impressed with the work she has done here in the lieutenant governor's office and would urge her to explore a run."
If you're dissatisfied with your dead-end job, watching this new Code.org video might push you over the edge and have you quitting before the end of the work day. The way professional coders like Mark Zuckerberg and Bill Gates (who have made billions typing out ones and zeros) talk about it, coding is the most creatively fulfilling job you could have.
The video, posted by the computer education nonprofit Code.org, features shots of Facebook's incredible offices and cameos from Miami Heat center Chris Bosh and The Black Eyed Peas' Will.i.am. (Money quote from the singer: "Great coders are today's rockstars.") It's all quite glamorous, and it's a far cry from the "code monkey" image that some Americans probably have of coders. Computer programmers are no longer wearing suits and languishing in cubicles, they're running around Facebook's gorgeous Menlo Park campus wearing hoodies, instead, and making tons of money.
The reality is that coding is generally not much more glamorous than any other job, but it's also not a career path that many young people consider. Making computer engineering alluring certainly can't hurt, especially since there seems to be so many vacant coding jobs out there.
With that in mind, the video saves their most important point for last: "1 million of the best jobs in America may go unfilled... because only 1 in 10 schools teach students how to code." Code.org promotes free online coding programs and encourages people to fight to get coding taught in schools across America.
Wolf in sheep's clothing: Uncovering how deadly bacteria trick the immune system Public release date: 28-Feb-2013 [ | E-mail | Share ]
Contact: Rachel Champeau rchampeau@mednet.ucla.edu 310-794-2270 University of California - Los Angeles Health Sciences
UCLA study could provide insight into recent TB outbreak in L.A.'s skid row
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-gammatriggered 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.
###
The study was funded by the National Institute of Arthritis and Musculoskeletal Skin Diseases, part of the National Institutes of Health (NIH P50; ARO63020; RO1s AI022553, AR040312 and AI047868; and CTSA Grant UL1TR000124).
Additional authors are listed in the manuscript.
For more news, visit the UCLA Newsroom and follow us on Twitter.
-UCLA-
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Wolf in sheep's clothing: Uncovering how deadly bacteria trick the immune system Public release date: 28-Feb-2013 [ | E-mail | Share ]
Contact: Rachel Champeau rchampeau@mednet.ucla.edu 310-794-2270 University of California - Los Angeles Health Sciences
UCLA study could provide insight into recent TB outbreak in L.A.'s skid row
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-gammatriggered 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.
###
The study was funded by the National Institute of Arthritis and Musculoskeletal Skin Diseases, part of the National Institutes of Health (NIH P50; ARO63020; RO1s AI022553, AR040312 and AI047868; and CTSA Grant UL1TR000124).
Additional authors are listed in the manuscript.
For more news, visit the UCLA Newsroom and follow us on Twitter.
-UCLA-
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
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Public release date: 28-Feb-2013
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