{"id":477843,"date":"2024-01-05T17:13:45","date_gmt":"2024-01-05T22:13:45","guid":{"rendered":"https:\/\/platohealth.ai\/uofl-researchers-are-unmasking-an-old-foes-tricks-to-thwart-new-diseases\/"},"modified":"2024-01-05T22:00:27","modified_gmt":"2024-01-06T03:00:27","slug":"uofl-researchers-are-unmasking-an-old-foes-tricks-to-thwart-new-diseases","status":"publish","type":"post","link":"https:\/\/platohealth.ai\/uofl-researchers-are-unmasking-an-old-foes-tricks-to-thwart-new-diseases\/","title":{"rendered":"UofL researchers are unmasking an old foe\u2019s tricks to thwart new diseases","gt_translate_keys":[{"key":"rendered","format":"text"}]},"content":{"rendered":"
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When the body encounters bacteria, viruses or harmful substances, its innate immune cells, neutrophils, assemble at the site to combat the invader.<\/p>\n

Credit: UofL photo.<\/p>\n

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When the body encounters bacteria, viruses or harmful substances, its innate immune cells, neutrophils, assemble at the site to combat the invader.<\/p>\n

Bacteria and viruses have ways to avoid these defenses, however. Yersinia pestis<\/em>, the bacteria that causes bubonic and pneumonic plague, for example, can hide from the immune system, allowing it to replicate in the body unhindered until it can overwhelm the host. This ability allowed Y. pestis<\/em> to spread bubonic plague across Europe in the 14th<\/sup> Century, killing a third of the European population.<\/p>\n

While plague may not be a serious threat to human health in modern times, researchers at the University of Louisville are studying Y. pestis<\/em> to better understand its ability to evade the immune system and apply that understanding to control other pathogens.<\/p>\n

\u201cIf you look at human plague, people don\u2019t show symptoms right away even though they have an active infection because the bacteria is hiding from the immune system. Then all of a sudden there is a lot of bacteria, the immune system is overwhelmed and in the case of pneumonic plague, the individual dies from pneumonia,\u201d said Matthew Lawrenz, professor in the UofL Department of Microbiology and Immunology.<\/p>\n

Neutrophils are the immune system\u2019s first responders, sending out protein molecules to summon other neutrophils to attack and destroy the invader. Among the first molecules sent out by neutrophils to signal an infection are Leukotriene B4 (LTB4) lipid molecules. Y. pestis<\/em> interferes with the immune response by suppressing the LTB4 signals. Lawrenz has received a new $2.9 million, four-year grant from the National Institutes of Health to investigate how Y. pestis<\/em> blocks LTB4. Ultimately, he expects this understanding will lead to ways to prevent Y. pestis<\/em> from blocking the signals and hopefully, apply that understanding to other types of infections.<\/p>\n

\u201cThis historic pathogen is really good at manipulating the immune system, so we use it as a tool to better understand how white blood cells like neutrophils and macrophages respond to bacterial infection,\u201d Lawrenz said. \u201cIn this project, we are using Yersinia<\/em> to better understand why LTB4 is so important to controlling plague. This understanding would apply to almost any infection of the lungs or other areas, and it probably could apply to viruses also.\u201d<\/p>\n

A member of the UofL Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases,<\/u> Lawrenz has been studying plague bacteria for nearly two decades. His previous work includes discoveries of how Y. pestis<\/em> acquires iron and zinc to overcome a host\u2019s defense mechanism known as nutritional immunity and has increased understanding of how Y. pestis<\/em> inhabits spaces within host macrophages to hide from the immune system.<\/p>\n

Katelyn Sheneman, a doctoral student in Lawrenz\u2019s lab, also has received a prestigious $100,000 research award for trainees from the NIH. This grant will fund her research to understand how Y. pestis<\/em> changes the contents of extracellular vesicles, cellular containers produced by immune cells that contain proteins, lipids such as LTB4 and other components. These vesicles are released into the bloodstream to communicate to other cells what is happening in their part of the body, such as an infection.<\/p>\n

\u201cMy project is looking at how Y. pestis<\/em> alters the number of vesicles being produced, what is being packaged in them and how other cells are responding to them,\u201d Sheneman said. \u201cWe have some good evidence that pestis<\/em> is able to manipulate the production of these vesicles, so we are going to look at the role the vesicles play in pulmonary infection and how that influence contributes to overall systemic infection.\u201d<\/p>\n

Since there is no effective vaccine against infection by Y. pestis <\/em>and it has the potential to be used as a bioweapon, Lawrenz and Sheneman study Y. pestis<\/em> in UofL\u2019s Biosafety Level 3 facilities at the Regional Biocontainment Laboratory, part of a network of 12 regional and 2 national biocontainment laboratories for studying infectious agents. Biosafety Level 3 facilities are built to exacting federal safety and security standards in order to protect researchers and the public from exposure to the pathogens being investigated. <\/p>\n

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