Bacteria may play a surprising role in how the body responds to infections by causing pain and suppressing the immune system, according to a new study published in the journal Nature.
In studies involving laboratory mice, researchers at Boston Children’s Hospital discovered that the pain of invasive skin infections, caused by antibiotic-resistant Staphylococcus aureus, appears to be induced by the bacteria themselves and not by the body’s immune response.
Researchers also found that once pain neurons “sense” the invading bacteria, they suppress the immune system — potentially helping the bacteria become more virulent.
The findings could change the way doctors treat painful infections such as meningitis, urinary tract infections, intestinal infections, and tooth aches.
“If we could block pain in infected tissues and also block what pain neurons do to the immune system, it could help us treat bacterial infections better,” says lead author Isaac Chiu, PhD, a neuro-immunologist at Boston Children’s Neurobiology Program.
The study was launched after Chiu and co-author Christian A. Von Hehn, MD, were culturing sensory neurons and immune cells together in a dish to see how they interacted during an infection.
“Surprisingly, the neurons were responding immediately to the bacteria,” says Chiu.
That inspired them to move to a mouse study of skin infections, the first one to their knowledge ever used to study pain.
Their finding that pain neurons, once activated by bacteria, suppress the immune system was equally unexpected.
“I was thinking they would do the opposite,” says Chiu.
Why would pain neurons try to weaken the immune response? Chiu believes the neurons are trying to protect tissues from further damage caused by inflammation — a protective mechanism that bacteria might be exploiting to their advantage.
In the study, Chiu and his colleagues examined pain, tissue swelling, immune cell numbers and the number of live bacteria in mice with staphylococcal skin infections. They found that pain levels tracked closely with the number of live bacteria and peaked well before tissue swelling peaked. The team also says it documented “communication” between bacteria, pain neurons and key cells from the immune system.
“We found that major parts of the immune system are not necessary for pain during infection, but that bacteria themselves are the source of much of the pain,” said Chiu. “In treating pain during infection, we may need to think about how to block the pathogenic components themselves, and not just the immune/inflammatory pathways.”
“We also found that sensory neurons modulate the immune system after they’re activated. This suggests, though we haven’t yet been able to prove it, that the ability of virulent bacteria strains to cause pain may give them an advantage, by allowing them to use the neurons to suppress immunity.”
The researchers plan to explore the relationship between pain, bacteria, and the immune system further, and investigate new treatments to block pain caused by bacteria.
Antibiotic-resistant Staphylococcus aureus is responsible for several difficult-to-treat infections in humans. The bacterium has developed resistance to several antibiotics, including penicillin, and is especially troublesome in hospitals, prisons and nursing homes. Patients with open wounds, invasive devices, and weakened immune systems are at greater risk of infection.