肠道微生物 z-bo 2020-11-25 301

　　Researchers recently published a report in the journal Cell Reports that gut microbes stimulate antiviral signals in non-immune lung cells to defend against influenza viruses in the early stages of infection. The enhanced baseline type I interferon (IFNα/β) signal drives the antiviral response, reducing mouse influenza virus replication and weight loss, but this protective effect will be weakened with antibiotic treatment.

　　"This study supports the idea that inappropriate antibiotics not only promote antibiotic resistance and eliminate useful protective probiotics, but may also make you more susceptible to viral infections." This from the Francis Crick Institute in the United Kingdom Andreas Wack, the corresponding author of the study, said. "In some countries, the animal husbandry industry uses antibiotics in large quantities to prevent infection, so the treated animals may be more susceptible to viral infections."

　　IFNα/β signals play a central role in immune defense against viral infections. These approaches can be fine-tuned to obtain antiviral protection while avoiding tissue damage and inflammation. This balance is evident in individuals with genetic variations that lead to high interferon production. They can enhance the immune response to viruses, but on the other hand, they show signs of chronic auto-inflammation. It is still unclear how IFNα/β signaling regulates this balance to simultaneously ensure minimal inflammation and maximum antiviral protection.

　　To solve this problem, Wack and his team used mice that increased the expression of IFNα/β receptors due to mutations. These mice had increased baseline IFNα/β signals. These mice were more resistant to influenza virus infection, lost less weight, reduced viral gene expression 8 hours after infection, and reduced influenza virus replication two days later. In view of the early control of viral load, the subsequent IFNα/β signal and antiviral immune response were not fully initiated. The results show that regulating the expression level of IFNα/β receptors can precisely regulate the IFNα/β signal in the lungs.

　　The protective effect of baseline IFNα/β signal enhancement decreased after 2-4 weeks of antibiotic treatment, mainly in the IFNα/β signal of lung interstitial cells, which is a group of non-immune cells that make up structural tissues and organs. In contrast, stool transplantation reversed the susceptibility to influenza virus infection caused by antibiotics, which suggests that gut microbes may have played a role.

　　In general, the results show that the microbiota increases the IFNα/β signal of the lung interstitial cells, thereby improving the ability to resist influenza virus infection. This new finding is consistent with the results of previous studies, which showed that mice treated with oral antibiotics are more susceptible to viruses, including influenza A viruses.

　　Wack said: "This study and previous studies have shown that microbial-driven signals can work at multiple levels, inducing antiviral status in non-immune cells, controlling infection in the early stages of infection, and enhancing immune cell performance in the later stages of infection Features."

　　In the next step, the researchers plan to further study the exact origin and mechanism of microbe-driven antiviral resistance. "Previous research has shown that microbial-driven signals in lung stromal cells may come from the intestine or lungs," Wack said. However, in the study presented here, the results of the stool transplant experiment strongly suggest that the intestine is involved in this effect. We would love to know the exact nature of the signal from the intestine to the lungs, and we are studying several hypotheses. "