(Press-News.org) Contact information: Leila Gray
leilag@uw.edu
206-685-0381
University of Washington
TB bacteria mask their identity to intrude into deeper regions of lungs
Cell surface lipids hide molecular patterns that infection-killing cells might recognize as dangerous
TB-causing bacteria appear to mask their identity to avoid recognition by infection-killing cells in the upper airways. The bacteria call up more permissive white blood cells in the deeper regions of the lungs and hitch a ride inside them to get into the host's body.
Details on this finding are reported Dec. 16 in the advanced online edition of the journal Nature. The research was a collaboration between the University of Washington and the Seattle Biomedical Research Institute.
Dr. Lalita Ramakrishan, who studies how TB evades the body's immune system and manipulates the body's defenses for its own ends, is the senior author. She is a UW professor of microbiology, medicine and immunology. The lead author is C.J. Cambier of the UW Department of Immunology.
Ramakrishnan noted that the recent study also suggests an explanation for the longstanding observation that tuberculosis infections begin in the comparatively sterile lower lungs. In the upper respiratory tract, resident microbes and inhaled microbes of a variety of species signal their presence.
These tip-offs alert and attract many infection-fighting cells to the upper airways. The presence of other microbes in the upper airway may thereby help to keep TB infections at bay by creating a hostile environment.
Their presence may explain why TB is a less contagious disease than those caused by several other respiratory pathogens.
To cause disease, TB bacteria must sneak through this well-patrolled area and head for parts of the lungs where fewer microbiocidal cells are policing.
Almost like intruders wearing a stocking over their faces to keep surveillance cameras from clearly recording their features, the TB pathogens produce particular types of fatty substances, or lipids, on their cell surfaces.
These lipids, abbreviated as PDIM, are already known to be associated with bacterial virulence. The researchers showed that PDIM lipids function by masking the underlying molecular patterns that would reveal their dangerous nature to macrophages, a first-line defense of infection-fighting cells.
At the same time, a related lipid - called PGL - on the bacterium's cell surface promotes the recruitment of cells described as permissive macrophages. These clean-up cells engulf but don't kill the TB pathogens. Instead, they take them across the lung lining, deep into the lung tissue where the bacteria can establish an infection.
According to the researchers on this study, these mechanisms appear to allow certain TB pathogens to avoid detection by the pattern recognition receptors that enable some infection-fighting cells to spot a variety of different disease microbes through the pathogen-associated molecular patterns on or near their cell surface.
Like most other bacteria, TB pathogens have many of these telltale molecular patterns that should activate an immune response. However, TB pathogens have evolved mechanisms to circumvent tripping the alarm, in this case by physically masking the otherwise detectable pattern. This cover-up allows them to infect the airway initially by avoiding the infection-fighting cell populations that are detrimental to their survival, the researchers noted.
The TB pathogens then use the other lipid molecule, PGL, to co-opt a host chemical pathway that triggers the recruitment of the permissive macrophages.
The present study expands on earlier work in the Ramakrishan and collaborative labs, which helped describe the strategies by which TB pathogens manipulate host pathways for their own purposes after they enter certain host cells.
These include the secretion of proteins that help expand the niche for TB by recruiting macrophages to the early lung tubercles characteristic of the disease. The present study describes earlier stages in infection, when the pathogens first come in contact with their potential host at the surface of the lining of the lung.
"The current study suggests the manner in which the TB pathogens manipulate recruitment of the first responding macrophages to gain access to their preferred niche," the researchers noted.
"The choreographed entry involves two related TB cell lipids acting in concert to avoid one host pathway while inducing another," they wrote. The findings link the previously known, absolutely essential virulence factor on the surface of TB cells, PDIM, to the evasion of immune cell detection. They also might explain why a certain pathogen molecular pattern recognition system is dispensable in protecting against TB. On the other hand, PGL is not required on the surface of TB cells for them to infect the body.
Ramakrishnan noted that globally, a lot of samples of TB taken from infected patients do not have PGL. "However," she and her research team noted, "the importance of PGL in mediating TB virulence or transmission is underscored by its presence in many of the W-Beijing strains" of TB which are starting to rapidly appear in more patient samples, and which have predominated in outbreaks in North America.
Ramakrishnan explains that their findings suggest how PGL may play an important role in increasing TB's infectivity.
"The presence of PGL in ancestral strains of TB suggest it played an integral role in the evolution of TB infectivity," the researchers noted. "TB is an ancient disease and the enhanced infectivity conferred by PGL may have been essential for most of its history before human crowding, with its increased opportunity for transmission, made it dispensable."
The study findings, and previous work on TB, might also explain why smaller droplets of TB are more infectious than larger ones. Only the smaller droplets can make their way down into the lower airways. On the flip side, all it takes is 3 or fewer TB mycobacteria with PGL-producing ability to enter the lower lungs and start an infection.
INFORMATION:
The other researchers on the study, in addition to Cambier and Ramkrishnan, were Kevin K. Takaki, David M. Tobin, and Christina L. Cosma, all of the UW Department of Microbiology; Ryan Larson and Kevin N. Urdahl of the of the UW Department of Immunology and the Seattle Biomedical Research Institute. Urdahl also is from the UW Department of Pediatrics.
The research was supported by training and research grants from the National Science Foundation, American Lung Association, National Institutes of Health, and American Cancer Society. Tobin is an NIH New Innovator and Ramakrishnan is an NIH Pioneer.
TB bacteria mask their identity to intrude into deeper regions of lungs
Cell surface lipids hide molecular patterns that infection-killing cells might recognize as dangerous
2013-12-20
ELSE PRESS RELEASES FROM THIS DATE:
H. pylori vaccine shows promise in mouse studies
2013-12-20
H. pylori vaccine shows promise in mouse studies
Researchers from Southern Medical University in Guangdong, Guangzhou, China, have developed an oral vaccine against Helicobacter pylori, the bacteria responsible for peptic ulcers and some forms of gastric cancer, ...
New study shows that more than half of consumers will choose a health-care plan that costs too much
2013-12-20
New study shows that more than half of consumers will choose a health-care plan that costs too much
New research from Columbia Business School warns that consumers will make mistakes totaling $9 billion; offers prescriptions to help improve consumer experience using ...
In addiction, meditation is helpful when coupled with drug and cognitive therapies
2013-12-20
In addiction, meditation is helpful when coupled with drug and cognitive therapies
A new paper suggests that rehabilitation strategies coupling meditation-like practices with drug and behavior therapies are more helpful than drug-plus-talk therapy ...
Mating is the kiss of death for certain female worms
2013-12-20
Mating is the kiss of death for certain female worms
The presence of male sperm and seminal fluid causes female worms to shrivel and die after giving birth, Princeton University researchers reported this week in the journal Science. The demise of the female appears ...
Landscape architecture study places value on Klyde Warren Park, other urban spaces
2013-12-20
Landscape architecture study places value on Klyde Warren Park, other urban spaces
New research area tells entities what public projects are worth
A UT Arlington landscape architect and his graduate students have published three case studies for the 2013 Case ...
Telecoupling science shows China's forest sustainability packs global impact
2013-12-20
Telecoupling science shows China's forest sustainability packs global impact
As China increases its forests, a Michigan State University (MSU) sustainability scholar proposes a new way to answer the question: if a tree doesn't fall in China, can you hear it elsewhere ...
New ways to promote fitness for urban girls proposed by Rutgers-Camden nursing professor
2013-12-20
New ways to promote fitness for urban girls proposed by Rutgers-Camden nursing professor
Most people know that one of the keys to reducing or preventing health problems is to get more exercise, but determining how to best integrate physical activity into their ...
Disabled shoppers confront holiday shopping barriers
2013-12-20
Disabled shoppers confront holiday shopping barriers
Before chestnuts roast on the fire and sugarplums dance in the dreams of youngsters, the holiday season elicits visions of crowded parking lots and malls overrun by shoppers while retailers try to keep up with ...
Bullying in academia more prevalent than thought, says Rutgers-Camden scholar
2013-12-20
Bullying in academia more prevalent than thought, says Rutgers-Camden scholar
CAMDEN — Bullying isn't only a problem that occurs in schools or online among young people. It can happen anywhere to anyone, and a Rutgers–Camden nursing scholar is shedding some ...
CCNY chemists use sugar-based gelators to solidify vegetable oils
2013-12-20
CCNY chemists use sugar-based gelators to solidify vegetable oils
Mannitol and sorbitol dioctanoates could provide alternatives to trans fats linked to obesity, coronary artery disease and diabetes
Researchers at The City College of New York have reported the ...
LAST 30 PRESS RELEASES:
Inability to pay for healthcare reaches record high in U.S.
Science ‘storytelling’ urgently needed amid climate and biodiversity crisis
KAIST Develops Retinal Therapy to Restore Lost Vision
Adipocyte-hepatocyte signaling mechanism uncovered in endoplasmic reticulum stress response
Mammals were adapting from life in the trees to living on the ground before dinosaur-killing asteroid
Low LDL cholesterol levels linked to reduced risk of dementia
Thickening of the eye’s retina associated with greater risk and severity of postoperative delirium in older patients
Almost one in ten people surveyed report having been harmed by the NHS in the last three years
Enhancing light control with complex frequency excitations
New research finds novel drug target for acute myeloid leukemia, bringing hope for cancer patients
New insight into factors associated with a common disease among dogs and humans
Illuminating single atoms for sustainable propylene production
New study finds Rocky Mountain snow contamination
Study examines lactation in critically ill patients
UVA Engineering Dean Jennifer West earns AIMBE’s 2025 Pierre Galletti Award
Doubling down on metasurfaces
New Cedars-Sinai study shows how specialized diet can improve gut disorders
Making moves and hitting the breaks: Owl journeys surprise researchers in western Montana
PKU Scientists simulate the origin and evolution of the North Atlantic Oscillation
ICRAFT breakthrough: Unlocking A20’s dual role in cancer immunotherapy
How VR technology is changing the game for Alzheimer’s disease
A borrowed bacterial gene allowed some marine diatoms to live on a seaweed diet
Balance between two competing nerve proteins deters symptoms of autism in mice
Use of antifungals in agriculture may increase resistance in an infectious yeast
Awareness grows of cancer risk from alcohol consumption, survey finds
The experts that can outsmart optical illusions
Pregnancy may reduce long COVID risk
Scientists uncover novel immune mechanism in wheat tandem kinase
Three University of Virginia Engineering faculty elected as AAAS Fellows
Unintentional drug overdoses take a toll across the U.S. unequally, study finds
[Press-News.org] TB bacteria mask their identity to intrude into deeper regions of lungsCell surface lipids hide molecular patterns that infection-killing cells might recognize as dangerous