• Flu fighters
• Lung protection
What is already known on this topic
Interferon α/β signaling triggers antiviral protection while avoiding tissue damage due to inflammation. But how these signaling pathways strike the right balance between maximizing antiviral protection and minimizing excessive inflammation is unclear.
What this research adds
Signals from gut bacteria help to maintain a first line of defense in the lining of the lung, protecting mice against the influenza virus. When rodents with healthy gut bacteria were infected with influenza virus, around 80% of them survived. But only a third of the animals survived if they were given antibiotics before being infected.
The findings support previous studies showing that mice treated with oral antibiotics are more susceptible to viral infections, and show that gut bacteria help to keep non-immune cells prepared to fight off infections.
Signals from gut bacteria help to maintain a first line of defense in the lining of the lung, protecting mice against the influenza virus. That’s according to a new study, published in the journal Cell Reports, which highlights how antibiotics can leave the lung vulnerable to flu viruses.
Interferon α/β (IFN α/β) signaling plays a key role in helping the immune system fight off viral infections. These immune pathways trigger antiviral protection while avoiding tissue damage due to inflammation. However, IFN activity must be finely controlled, as people with a genetic variant that results in high IFN production can mount enhanced immune responses against viruses, but they show signs of chronic inflammation.
How the IFNα/β signaling pathway strikes the right balance between maximizing antiviral protection and minimizing excessive inflammation is unclear. So Konrad Bradley, Katja Finsterbusch and their colleagues at the Francis Crick Institute in London set out to look at mice with a mutation that increases the levels of the IFNα/β receptor, resulting in enhanced IFNα/β signaling.
When infected with influenza virus, 80% of mice with healthy gut bacteria survived. Those with increased IFNα/β signaling were more resistant to influenza virus infection, and showed less weight loss, lower virus gene expression eight hours after infection, and reduced influenza virus replication two days later.
But when the researchers treated the mice with antibiotics for two to four weeks, the protective effect of increased IFNα/β signaling was reduced and only a third of the infected animals survived. Decreased IFNα/β signaling was observed mainly in non-immune cells that make up the lining of the lungs.
Giving fecal transplants to antibiotic-treated mice reversed their susceptibility to flu virus infection, which suggests a role for gut microbiota in controlling IFN signaling.
Next, the team found that the cells lining the lungs, rather than immune cells, were responsible for early flu resistance induced by gut bacteria. Indeed, microbiota-driven IFN signals keep antiviral genes in the lung lining active, preventing the virus from replicating in the lungs.
The findings show that gut bacteria help to keep non-immune cells prepared for fighting off infections by switching on antiviral genes even before the virus arrives, the scientists say.
The work also supports previous studies showing that mice treated with oral antibiotics are more susceptible to viral infections, adding further evidence that antibiotics should not be taken or prescribed lightly.