title: Influenza Virus Affects Intestinal Microbiota and Secondary Salmonella Infection in the Gut through Type I Interferons.
abstract: Human influenza viruses replicate almost exclusively in the respiratory tract, yet infected individuals may also develop gastrointestinal symptoms, such as vomiting and diarrhea. However, the molecular mechanisms remain incompletely defined. Using an influenza mouse model, we found that influenza pulmonary infection can significantly alter the intestinal microbiota profile through a mechanism dependent on type I interferons (IFN-Is). Notably, influenza-induced IFN-Is produced in the lungs promote the depletion of obligate anaerobic bacteria and the enrichment of Proteobacteria in the gut, leading to a "dysbiotic" microenvironment. Additionally, we provide evidence that IFN-Is induced in the lungs during influenza pulmonary infection inhibit the antimicrobial and inflammatory responses in the gut during Salmonella-induced colitis, further enhancing Salmonella intestinal colonization and systemic dissemination. Thus, our studies demonstrate a systemic role for IFN-Is in regulating the host immune response in the gut during Salmonella-induced colitis and in altering the intestinal microbial balance after influenza infection.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Elisa
authors.initials: E
authors.lastname: Deriu
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Gayle M
authors.initials: GM
authors.lastname: Boxx
authors.affiliation: School of Dentistry, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Xuesong
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Human Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Calvin
authors.initials: C
authors.lastname: Pan
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Sammy David
authors.initials: SD
authors.lastname: Benavidez
authors.affiliation: School of Dentistry, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Lujia
authors.initials: L
authors.lastname: Cen
authors.affiliation: Department of Pathology and Laboratory Medicine, CURE Imaging and Stem Cell Biology Core, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Nora
authors.initials: N
authors.lastname: Rozengurt
authors.affiliation: School of Dentistry, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Genhong
authors.initials: G
authors.lastname: Cheng
mesh_terms: D000818:Animals; D060085:Coinfection / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D015151:Immunoblotting; D007370:Interferon Type I / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology
chemical_list: D007370:Interferon Type I