circleA lung infection, whether viral or bacterial, usually produces obvious symptoms such as weakness, difficulty breathing, and brain confusion. These signs signal others to keep a safe distance from the infected person. Pseudomonas aeruginosa various Lung infectionFrom mild bronchitis to life-threatening pneumonia, there are diseases that cause inflammation and tissue destruction even though they have no symptoms in the acute phase.1
in Chronic infectionThese bacteria form a biofilm, an extracellular polymer matrix, around themselves to protect them from antimicrobial agents, enzymes, and neutrophils.2 Now, cellA group of scientists investigated the underlying mechanism and reported that biofilms are the culprit. Pseudomonas It clears the bacteria from the mice’s sensory neurons, preventing signals from reaching the brain and reducing disease symptoms.3 These findings provide a greater understanding of how biofilm-forming bacteria evade the lung-to-brain pathway, a potentially important tactic in persistent infection.
After pulmonary infection with non-biofilm-forming bacteria, neurons in the paraventricular nucleus (PVN) were activated (green, nuclei stained blue).
Parisa Moazen and Deborah Krulash, University of Calgary, Canada.
About 10 years ago, Ellis Glanton“I think it’s important to be aware of the effects of the immune system,” said Dr. Pseudomonas aeruginosa “I thought this was pretty straightforward,” he said, using two mutant strains of the bacteria, one that formed biofilms and one that didn’t, in mice’s lungs. Brian Yip“We couldn’t pinpoint exactly why some mice got sick without the biofilm and others with the biofilm didn’t get sick at all,” added Yip, a physician and immunologist at the University of Calgary and co-author of the study. Because the team knew that neutrophils could sense bacteria with or without a biofilm, they began looking beyond the immune system. “Maybe the biofilm is hiding the bacteria. What is it hiding?” Yip wondered.
Pseudomonas The bacteria (green) affect how lung sensory neurons communicate via the vagus nerve to the PVN in the hypothalamus.
Jesse Horn.
Previous studies have shown that one of the bacteria’s main toxins, a surface molecule, Lipopolysaccharide (LPS)The bacteria that cause inflammation and other symptoms are protected by biofilm components.4 To understand how exposure to LPS causes illness, the team investigated the role of the LPS receptor, Toll-like receptor 4 (TLR4). Mice lacking the pain sensory neuron TLR4 had reduced hypothermia and overall sickness scores when infected with non-biofilm-forming bacteria. To elucidate this further, the researchers TLR4 They injected TLR4 into lung nociceptive neurons and exposed the cells to bacteria that do not form biofilms.Mice with intact TLR4 showed characteristic disease symptoms, whereas mice lacking the receptor showed greatly reduced disease symptoms.
The turning point came Luke BrownYip, a doctoral student at the University of Calgary and co-author of the study, also worked on the project. After finding that sensory neurons could “see” bacteria, Yip and his team wondered whether this interaction might send signals to the brain that could trigger behavioral changes. They Deborah Crash and Jaideep BainsBehavioral neuroscientists at the University of Calgary conducted a study to find the answer to this question.
“[We] “They asked, ‘Are we completely crazy?'” Yip recalls. “And immediately, people who knew about stress response and behavior said it was probably the hypothalamus and these neurons. To them, it made perfect sense!”
Following this thread, the team looked at the hypothalamus and found that mice that had been given LPS had more active corticotropin-releasing hormone (CRH) neurons in their lungs than mice that had not been given LPS. TLR4 Intraneuron. CRH neuron Responding to stress Modify your behavior accordingly.5 Inhibiting the activity of CRH neurons in mice given non-biofilm bacteria alleviated symptoms.
Biofilms mask bacteria from detection by pulmonary sensory neurons, limiting disease symptoms (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, which mediates the disease phenotype (right).
Jesse Horn
“We’re only just beginning to understand how the brain recognizes that there’s an infection in the body. What’s exciting is that we now appear to have a wide variety of neurons that can detect different pathogens and send signals to the brain to induce disease,” he said. Stephen Liberlessa neuroscientist at Harvard Medical School who was not involved in the study.
The team next plans to study different types of lung infections and their interactions with the nervous and immune systems. “We’re thinking in a totally different way: How many neurological processes, mood, and definable pathological disorders can result from something that gets into the lungs and activates the nervous system,” Yip said.
