Lungs Alert Brain of Infections, Leading to Behavior Changes

Researchers have discovered an innovative process in which the lungs communicate directly with the brain about infections, challenging conventional beliefs about how the body responds to sickness. This research, carried out on mice, shows that neurological pathways play a crucial role in causing symptoms of illness, not just immune reactions.

These results indicate that treating respiratory infections and long-term lung issues may necessitate strategies that address both the nervous system and the pathogen.

Furthermore, the study noted a contrast in sickness behavior between genders, which could explain the phenomenon of the “man flu,” as males seem to rely more heavily on neuronal signals during times of illness.

Key Facts:

1. Direct Lung-Brain Communication: The lungs use neurons involved in the pain pathway to alert the brain about infections, leading to symptoms of sickness through nervous system activation rather than solely through the immune response.
2. Implications for Treatment: Understanding this lung-brain dialogue opens possibilities for dual treatment strategies that address both the infection and its neurological impact, offering hope for better management of respiratory conditions.
3. Gender Differences in Sickness Response: The study found male mice showed more severe sickness behaviors than females under the same conditions, suggesting neuronal communication plays a more significant role in males, shedding light on gender disparities in illness experiences.

University of Calgary researchers have discovered the lungs communicate directly with the brain when there is an infection. Findings show the brain plays a critical role in triggering the symptoms of sickness, which may change the way we treat respiratory infections and chronic conditions.  

Dr. Bryan Yipp, MD ’05, MSc’05, a clinician researcher at the Cumming School of Medicine and the senior author of the study, explains that the lungs utilize the same sensors and neurons in the pain pathway to communicate the presence of an infection to the brain.

This communication prompts the manifestation of symptoms associated with illness, such as a general feeling of being unwell, fatigue, and loss of appetite. This significant finding suggests that in addition to treating the infection itself, it may be necessary to address the nervous system as well.

Prior to this study, conducted in mice, it was thought infections in the lungs and pneumonia induce inflammatory molecules that eventually made their way to the brain through the blood stream. This makes the lungs alert brain of infections.

Sickness was thought to be a consequence of the immune system kicking into action. However, findings reveal that sickness results from nervous system activation in the Lungs alert brain of infections.

Understanding the lung-brain dialogue is important for treatment because bacteria that cause lung infections can produce a biofilm, a coating to surround themselves so the nervous system can’t see them. That allows the bug to hide out in the lungs for a long time, which may shed light across diverse serious lung infections that are less symptomatic.

For example, an unexplained anomaly Yipp witnessed in the intensive care unit (ICU) during COVID. The phenomenon, coined “happy hypoxia”, was being recorded in ICUs throughout the world.

“We would have patients whose oxygen levels were extremely low and x-rays confirmed they may need to be put on life support. Yet, when I went to see the patient, they would say I feel fine,” says Yipp.

“These people were experiencing limited sickness symptoms even though the virus was aggressively damaging their lungs.”

Yipp says understanding the lung brain communication pathways may also have broad implications for people with chronic lung infections like cystic fibrosis (CF). Many people with CF have a biofilm bacterium in their lungs and are asymptomatic. They feel okay, but then have a flare where they can become very ill. The reason for the flare can’t always be traced.

“It is possible the flare is also neurological that these people live asymptomatically because bacteria are hiding out,” says Yipp.

The findings, published in Cell, are the work of an interdisciplinary team including experts in neurobiology, microbiology, immunology, and infectious disease.

“Physician specialties are usually based on individual organs, with pulmonologists caring for the lungs and neurologists caring for the brain. Our study shows the lung is altering the brain and the brain is altering the organ. This intersection of communication is a different way of thinking about disease,” says Yipp.

The study conducted by University of Calgary researchers, including Drs. Christophe Altier, Joe Harrison, and Deborah Kurrasch, along with Dr. Jaideep Bains from the Krembil Research Institute in Toronto, reveals a fascinating connection between the brain and infections. It appears that there are intricate neural circuits involved, and targeting these neurocircuitry along with antibiotics could potentially help in managing infections and the resulting sickness.

Interestingly, the researchers also found that male mice exhibited more severe symptoms compared to females, despite having the same bacterial infection. This suggests that male sickness is more reliant on neuronal communications than females.

This discovery could provide support for the concept of “man flu,” where men are believed to exaggerate their sickness from respiratory infections. It turns out that their symptoms may not be exaggerated after all.

ALSO READ: World Water Day 22 March

Furthermore, the University of Calgary researchers have made another significant finding. They have discovered that the lungs directly communicate with the brain during an infection. This highlights the crucial role of the brain in triggering sickness symptoms, which could potentially revolutionize the treatment of respiratory infections and chronic conditions.

Dr. Bryan Yipp, a clinician researcher at the Cumming School of Medicine and the senior author of the study, explains that the lungs utilize the same sensors and neurons in the pain pathway to inform the brain about the presence of an infection. Consequently, the brain prompts the various symptoms associated with sickness, such as feeling unwell, tired, and experiencing a loss of appetite. This breakthrough suggests that in addition to treating the infection itself, it may be necessary to address the nervous system as well.

Prior to this study, conducted in mice, it was thought infections in the lungs and pneumonia induce inflammatory molecules that eventually made their way to the brain through the blood stream. Sickness was thought to be a consequence of the immune system kicking into action. However, findings reveal that sickness results from nervous system activation in the lung.

Understanding the lung-brain dialogue is important for treatment because bacteria that cause lung infections can produce a biofilm, a coating to surround themselves so the nervous system can’t see them. That allows the bug to hide out in the lungs for a long time, which may shed light across diverse serious lung infections that are less symptomatic.

For example, an unexplained anomaly Yipp witnessed in the intensive care unit (ICU) during COVID. The phenomenon, coined “happy hypoxia”, was being recorded in ICUs throughout the world.

“We would have patients whose oxygen levels were extremely low and x-rays confirmed they may need to be put on life support. Yet, when I went to see the patient, they would say I feel fine,” says Yipp.

“These people were experiencing limited sickness symptoms even though the virus was aggressively damaging their lungs.”

Yipp says understanding the lung brain communication pathways may also have broad implications for people with chronic lung infections like cystic fibrosis (CF). Many people with CF have a biofilm bacterium in their lungs and are asymptomatic. They feel okay, but then have a flare where they can become very ill. The reason for the flare can’t always be traced.

The flare may also have a neurological component, allowing these individuals to live without symptoms because bacteria are concealed,” stated Yipp.

The results, which were published in Cell, were achieved by a diverse team of experts in neurobiology, microbiology, immunology, and infectious diseases.

“Typically, medical specialties focus on specific organs, such as pulmonologists treating the lungs and neurologists treating the brain. Our research demonstrates that the lung impacts the brain and vice versa. This crossroads of communication offers a new perspective on diseases,” explained Yipp.

“The brain is intricately linked to all bodily functions, and there are likely even more intricate circuits at play. We can now consider targeting neurocircuitry in addition to antibiotics to combat infections and the resulting illnesses.”

The study’s corresponding authors are Drs. Christophe Altier, PhD, Joe Harrison, PhD, and Deborah Kurrasch, PhD, from the University of Calgary, along with Dr. Jaideep Bains, PhD, from the Krembil Research Institute in Toronto.

MORE STORIES: “Biofilm exopolysaccharides alter sensory-neuron-mediated sickness during Lungs Alert Brain of infections

Furthermore, the researchers noted another interesting discovery. Male mice exhibited more severe symptoms than females despite having the same bacterial infection. The study revealed that male sickness was more influenced by neuronal communication than that of females.

Yipp suggested that this finding may support the concept of the “man flu,” a term used informally to describe men who are believed to exaggerate their symptoms during respiratory infections. It appears that their symptoms may not be exaggerated after all.