What is already known
Respiratory viruses such as influenza A viruses and SARS-CoV-2 can cause severe disease. However, the outcomes of these respiratory infections vary widely among individuals. The gut microbiota may be in part responsible for this variability, as gut bacteria have been implicated in many inflammatory diseases and associated immune responses.
What this research adds
Working in mice, researchers found that segmented filamentous bacteria (SFB) — a type of bacteria found in the gut — protects mice against infection with influenza virus. This protection also applied to respiratory syncytial virus and SARS-CoV-2, and it required the presence of immune cells called alveolar macrophages in the lung. Further experiments showed that alveolar macrophages disabled influenza virus by activating a component of the immune system called the complement system.
Conclusions
The results reveal that the severity of respiratory infections depends at least in part on a complex interplay between the gut microbiota and the immune system. If applicable to humans, the findings could help assess whether people with respiratory infections might advance to severe disease.
Respiratory viruses such as influenza and SARS-CoV-2, the virus that causes COVID-19, can result in severe disease. However, the outcomes of these respiratory infections vary widely among individuals. New research shows that a type of bacteria found in the gut protects mice against infection with influenza and other respiratory viruses.
The results, published in Cell Host & Microbe, reveal that the severity of respiratory infections depends at least in part on a complex interplay between the gut microbiota and the immune system. If applicable to humans, the findings could help assess whether people with respiratory infections might advance to severe disease.
“We find it remarkable that the presence of a single common commensal bacterial species, amidst the thousands of different microbial species that inhabit the mouse gut, had such strong impacts in respiratory virus infection models,” says study co-senior author Richard Plemper at Georgia State University in Atlanta.
Scientists suspect that gut microbes may be in part responsible for the variability observed in the clinical outcomes of people with respiratory infections, as gut bacteria have been implicated in many inflammatory diseases and associated immune responses. What’s more, previous studies have shown that wild mice have activated immune systems, which make them relatively resistant to infection with influenza A virus.
Plemper and his colleagues set out to assess whether — and how — differences in specific microbial species can impact outcomes of respiratory viral infections in mice.
Microbiota differences
The researchers compared proneness to influenza infection in mice with defined differences in their gut microbiota composition. Disease symptoms and viral load in the animals’ lungs were measured several days after infection with influenza A virus.
Mice free of specific pathogens showed reduced viral loads in the lungs compared with “excluded flora” mice, which lack a panel of disease-modulating commensal microbes. These results suggest that one or more of the microbes absent in “excluded flora” mice might confer protection against influenza.
Of the microbes known to be excluded in these mice, segmented filamentous bacteria (SFB) — a type of bacteria found in the gut — stood out as a potential modulator of susceptibility to influenza infection. “SFB is a major contributor to, albeit not the sole mediator of, spontaneous resistance of mice to rotavirus, an intestinal pathogen, that arose in some mouse colonies,” the researchers say.
Immune activation
The protection against infection also applied to respiratory syncytial virus and SARS-CoV-2, and it required the presence of immune cells called alveolar macrophages in the lung, the researchers found.
In mice lacking SFB, alveolar macrophages were quickly depleted as respiratory virus infection progressed. In contrast, the alveolar macrophages of mice with SFB were able to prevent flu-triggered depletion and inflammatory signaling. Further experiments showed that alveolar macrophages disabled influenza virus by activating a component of the immune system called the complement system.
“We find it highly unlikely that segmented filamentous bacteria are the only gut microbes capable of impacting the phenotype of alveolar macrophages, and consequently, proneness to respiratory virus infection,” says study co-senior author Andrew Gewirtz. “Rather, we hypothesize that gut microbiota composition broadly influences proneness to respiratory virus infection. Microbiota mediated programming of basally resident alveolar macrophages may not only influence the severity of acute respiratory virus infection, but may also be a long-term post-respiratory virus infection health determinant.”
