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Jul 8, 2014

How Commensal Bacteria Turn Deadly

  • Scientists at the University of Liverpool’s Institute of Infection and Global Health say they made a major advance in understanding how the bacterium that causes pneumonia, meningitis, and septicemia usually remains harmlessly in the nose and throat.

    Streptococcus pneumoniae is a commensal bacterium, which lives in the nasopharynx as part of the body's natural bacterial flora. However, in the very young and old it can invade the rest of the body, leading to serious diseases such as pneumonia, sepsis, and meningitis, which claim up to a million lives every year worldwide. However, the conditions that drive this bacterium from harmless commensal to major pathogen are not understood. Researchers at the university believe they have now uncovered the mechanisms by which this occurs and how it is regulated by the host immune system.

    The team found that T regulatory cells are activated by the pneumococcus and move to dampen down a damaging pro-inflammatory response from the host immune system. When white blood cells attack bacteria they cause inflammation and, if this inflammation is uncontrolled, it can become excessive and damage host tissues, allowing the bacteria to spread into the rest of the respiratory system and other organs in the body.

    The first author of the study (“Density and Duration of Pneumococcal Carriage Is Maintained by Transforming Growth Factor b1 and T Regulatory Cells”), which was published in the American Journal of Respiratory and Critical Care Medicine, Daniel Neill, Ph.D., said: “These bacteria are quite happy to live in your nose and it's not in their interests to spread and kill their host. This is why they activate T regulatory cells: to keep the immune system in check and ensure their own survival. Our findings suggest induction of T regulatory cell responses in the upper airways reduces the risk of inflammatory damage that could lead to bacterial invasion and the development of disease.”

    Understanding this process can now lead scientists to investigate how the bacteria go from this state to causing lethal infections, he pointed out.

    “Vaccines are an essential part of our fight against this disease and have been highly successful,” added Aras Kadioglu, Ph.D., senior author of the study. “However, they do not protect us against all strains of pneumococci. Therefore, understanding the key immunological interactions with the pneumococcus in the very first site they enter and colonize the human body is crucial to future development of better vaccines.”

    In the study, according to Dr. Kadioglu, the group showed how there is a delicate balance between the ability of the pneumococcus to colonize the host nasopharynx and the critical need of the immune system to prevent damaging inflammation in this key site.

    “We identify the induction of active transforming growth factor (TGF)-β1 by S. pneumoniae in human host cells and highlight the key role for TGF-β1 and T regulatory cells in the establishment and maintenance of nasopharyngeal carriage in mice and humans,” wrote the investigators. “We identify the ability of pneumococci to drive TGF-β1 production from nasopharyngeal cells in vivo and show that an immune tolerance profile, characterized by elevated TGF-β1 and high nasopharyngeal T regulatory cell numbers, is crucial for prolonged carriage of pneumococci. Blockade of TGF-β1 signaling prevents prolonged carriage and leads to clearance of pneumococci from the nasopharynx. These data explain the mechanisms by which S. pneumoniae colonize the human nasopharynx without inducing damaging host inflammation and provide insight into the role of bacterial and host constituents that allow and maintain carriage.”

    “We hope that this will lead to developing novel therapies based on modulating the host immune system to prevent subsequent invasive disease,” said Dr. Kadioglu.


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