title: TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination.
abstract: Systems biological analysis of immunity to the trivalent inactivated influenza vaccine (TIV) in humans revealed a correlation between early expression of TLR5 and the magnitude of the antibody response. Vaccination of Trl5(-/-) mice resulted in reduced antibody titers and lower frequencies of plasma cells, demonstrating a role for TLR5 in immunity to TIV. This was due to a failure to sense host microbiota. Thus, antibody responses in germ-free or antibiotic-treated mice were impaired, but restored by oral reconstitution with a flagellated, but not aflagellated, strain of E. coli. TLR5-mediated sensing of flagellin promoted plasma cell differentiation directly and by stimulating lymph node macrophages to produce plasma cell growth factors. Finally, TLR5-mediated sensing of the microbiota also impacted antibody responses to the inactivated polio vaccine, but not to adjuvanted vaccines or the live-attenuated yellow fever vaccine. These results reveal an unappreciated role for gut microbiota in promoting immunity to vaccination.
authors.affiliation: Emory Vaccine Center, Emory University, Atlanta, GA 30329, USA; Yerkes National Primate Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Jason Z
authors.initials: JZ
authors.lastname: Oh
authors.affiliation: Emory Vaccine Center, Emory University, Atlanta, GA 30329, USA; Yerkes National Primate Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ravindran
authors.affiliation: Center for Inflammation, Immunity, and Infection, Georgia State University, Atlanta, GA 30302, USA.
authors.forename: Benoit
authors.initials: B
authors.lastname: Chassaing
authors.affiliation: Center for Inflammation, Immunity, and Infection, Georgia State University, Atlanta, GA 30302, USA; INSERM U1107, Universite d'Auvergne, 63001 Clermont-Ferrand Cedex 1, France.
authors.forename: Frederic A
authors.initials: FA
authors.lastname: Carvalho
authors.affiliation: Emory Vaccine Center, Emory University, Atlanta, GA 30329, USA; Yerkes National Primate Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Mohan S
authors.initials: MS
authors.lastname: Maddur
authors.affiliation: National Gnotobiotic Rodent Resource Center, University of North Carolina, Chapel Hill, NC 27514, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Bower
authors.affiliation: Yerkes National Primate Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Hakimpour
authors.affiliation: Emory Vaccine Center, Emory University, Atlanta, GA 30329, USA; Yerkes National Primate Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Kiran P
authors.initials: KP
authors.lastname: Gill
authors.affiliation: Department of Pathology, School of Medicine, Emory University, Atlanta, GA 30329, USA; Department of Clinical and Toxicological Analyses, Institute of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil.
authors.forename: Helder I
authors.initials: HI
authors.lastname: Nakaya
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
authors.forename: Felix
authors.initials: F
authors.lastname: Yarovinsky
authors.affiliation: National Gnotobiotic Rodent Resource Center, University of North Carolina, Chapel Hill, NC 27514, USA.
authors.forename: R Balfour
authors.initials: RB
authors.lastname: Sartor
authors.affiliation: Center for Inflammation, Immunity, and Infection, Georgia State University, Atlanta, GA 30302, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Gewirtz
authors.affiliation: Emory Vaccine Center, Emory University, Atlanta, GA 30329, USA; Yerkes National Primate Center, Emory University, Atlanta, GA 30329, USA; Department of Pathology, School of Medicine, Emory University, Atlanta, GA 30329, USA. Electronic address: bpulend@emory.edu.
authors.forename: Bali
authors.initials: B
authors.lastname: Pulendran
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D005408:Flagellin / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D011054:Poliovirus Vaccine, Inactivated / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051198:Toll-Like Receptor 5 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D022341:Yellow Fever Vaccine / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D011054:Poliovirus Vaccine, Inactivated; D051198:Toll-Like Receptor 5; D022341:Yellow Fever Vaccine; D005408:Flagellin