femaleWhen someone has a lung infection, whether viral or bacterial, they usually show telltale signs such as weakness, shortness of breath, and brain fog. These indicators signal others to keep a safe distance from contagious individuals. However, Pseudomonas aeruginosa It can cause a wide range of problems Lung infectionFrom mild bronchitis to life-threatening pneumonia, they cause acute, asymptomatic but severe inflammation and tissue destruction.1
~ inside Chronic infectionThese bacteria form a biofilm around themselves of an extracellular polymer matrix that protects them from antimicrobial agents, enzymes, and neutrophils.2 Now, in a published paper, CellA group of scientists investigated the underlying mechanisms and reported that biofilms are hidden. Pseudomonas Removing the bacteria from the sensory neurons of mice prevented signals from reaching the brain, alleviating disease symptoms.3 These findings provide a deeper understanding of how biofilm-forming bacteria evade communication channels between the lungs and the brain, a strategy that may be critical in persistent infections.
After lung infection with non-biofilm-forming bacteria, neurons in the superior ventricular nucleus (PVN) are activated (green; nuclei stained blue).
Parisa Moazen, Deborah Kurash, University of Calgary, Canada.
Almost 10 years ago, Ellis GrantonNow a physician and immunologist at the University of Calgary and co-author of the study, he tested the effects of: Pseudomonas aeruginosa We used two variants to test in mouse lungs, one that formed biofilms and one that did not. “We thought this would be pretty simple,” he said. Brian Whip“We couldn’t figure out exactly why some mice got sick without biofilms and the biofilm mice didn’t get sick at all,” he added. Knowing that neutrophils can detect bacteria, whether or not they have biofilms, the team began looking beyond the immune system. “Maybe the biofilms are hiding the bacteria. What are they hiding?” Yipp wondered.
Pseudomonas Bacteria (green) affect how lung sensory neurons communicate with the PVN of the hypothalamus via the vagus nerve.
Jesse Horn.
Previous studies have shown that one of the major bacterial toxins, a surface molecule, Lipopolysaccharide (LPS)Substances that cause inflammation and other symptoms are protected by biofilm components.4 To understand how LPS exposure causes disease, the research team studied the role of the LPS receptor, Toll-like receptor 4 (TLR4). Mice lacking TLR4 in their pain-sensing neurons showed reduced hypothermia and overall disease scores when infected with non-biofilm-forming bacteria. To learn more, the researchers specifically TLR4 In lung nociceptive neurons, cells were exposed to non-biofilm-forming bacteria. Mice with intact TLR4 showed characteristic disease symptoms, but mice lacking the receptor showed a significant reduction in disease symptoms.
When did the turning point come? Luke Browna PhD student at the University of Calgary and co-author of the study, participated in the project. After learning that sensory neurons could “see” bacteria, Yipp and his team wondered how this interaction could signal the brain to change behavior. They Deborah Kurash and Jaideep BainesBehavioural neuroscientists at the University of Calgary set out to find answers to these questions.
“[We] “I asked them, ‘Are we completely crazy?’” Yipp recalled. “And pretty quickly, they said that it’s probably the hypothalamus and these neurons that are invested in the stress response and behavior. It made perfect sense to them!”
As a follow-up to this thread, the team examined the hypothalamus and found that control mice treated with LPS had more activity in CRH (corticotropic hormone) neurons compared to mice lacking the hormone. TLR4 In neurons. CRH neurons cope with stress And then modify your behavior accordingly.5 When the activity of CRH neurons was blocked in mice treated with non-biofilm bacteria, the mice’s symptoms were alleviated.
Biofilms mask bacteria from detection by pulmonary sensory neurons, causing limited disease (left). In the absence of biofilms, pulmonary sensory neurons detect bacteria via TLR4 and LPS and signal via the vagus nerve to the PVN in the hypothalamus. PVN neurons are activated and release CRH, mediating the disease phenotype (right).
Jessie Horn
“We’re starting to understand how the brain recognizes that there’s an infection in the body. What’s interesting is that it now seems like there are different types of neurons that can detect different types of pathogens and send signals to the brain that can cause disease,” he said. Steven LiberesA neuroscientist at Harvard Medical School who was not involved in the study.
Next, the team will study different types of lung infections and their interactions with the nervous and immune systems. “We’re thinking in a completely different way: How many neurological processes, moods, definable pathological diseases can be triggered by substances that enter the lungs and activate the nervous system?” Yipp said.
