Researchers at the Center for Translational Antiviral Research within the Institute for Biomedical Sciences at Georgia State University have found that the composition of the gut microbiota affects the susceptibility of mice to respiratory viruses. virus Infections and the severity of these infections.
The findings, published in the journal cell host and microbeReport that segmented filamentous bacteria, a bacterium species Found in the intestines, mice were protected from influenza virus infection when these bacteria were either obtained naturally or administered.
This protection against infection also applies to respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2.SARS-CoV-2), the virus that causes COVID-19, To maintain this protection, the study says, the segmented filamentous bacteria require immune cells in the lungs originally called resident alveolar macrophages.
Study findings
In this study, researchers examined how differences in specific microbial species may influence the outcomes of respiratory virus infections and how they do so, which has not been previously well defined. They studied mice with different microbiome differences and the mice differed only in the presence or absence of segmented filamentous bacteria. Viral titers in the lungs were measured several days after infection and varied significantly depending on the nature of the microbiome of different animal groups.
“These findings highlight the complex interactions that fundamentally link the intestinal microbiota to the functionality of resident alveolar macrophages and the severity of respiratory virus infections,” said Dr. Andrew Gewirtz, co-senior author of the study and Regents Professor in the Institute for Biomedical Sciences. Are.” Science at Georgia State.
The study found that in segmented filamentous bacteria-negative mice, native alveolar macrophages were rapidly depleted as respiratory virus infection increased. However, in segmented filamentous bacteria-colonized mice, native alveolar macrophages were altered to lack influenza virus infection and resist inflammatory signaling.
Originally resident alveolar macrophages largely inactivated influenza viruses by activating a component of the immune system referred to as the complement system.
Implications and future directions
“We find it remarkable that among the thousands of different microbial species living in the mouse gut, the presence of a single common commensal bacterial species had such a strong effect in a respiratory virus infection model and that such effects were largely dependent on the native were responsible for the reprogramming of alveolar macrophages,” said Dr. Richard Plemper, co-senior author of the study, Regents Professor and director of the Center for Translational Antiviral Research at Georgia State. “If applicable to human infection, “These findings will have major implications for patient risk assessment for future progression to serious disease.”
“We find it highly unlikely that segmented filamentous bacteria are the only gut microbe that is able to influence the phenotype of alveolar macrophages, and, as a result, the susceptibility to respiratory virus infection,” Gewirtz said. “Rather, we hypothesize that gut microbiota composition broadly influences the susceptibility to respiratory virus infection. Microbiota mediated programming of native alveolar macrophages may not only influence the severity of acute respiratory virus infection but may also be a health determinant of long-term respiratory virus infection.
Reference: “Intestinal microbiota programming of alveolar macrophages influences the severity of respiratory viral infections” Wu L. Ngo, Caroline M. Lieber, He-Ji Kang, Kaori Sakamoto, Michal Kuczma, Richard K. By Plemper and Andrew T. Gewirtz, 30 January 2024, cell host and microbe,
DOI: 10.1016/j.chom.2024.01.002
The primary authors of the study are virologist Caroline M. Lieber of the Center for Translational Antiviral Research and immunologist Wu L. of the Institute for Biomedical Sciences at Georgia State. Were ngo. Other contributing authors were He-Ji Kang and Michael Kuczma of the Institute for Biomedical Sciences at Georgia State and Kaori Sakamoto of the University of Georgia.
The study is funded National Institutes of HealthNational Institute of Allergy and Infectious Diseases.