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Immunity. 2014 Sep 18;41(3):478-492. doi: 10.1016/j.immuni.2014.08.009. Epub 2014 Sep 11.

TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination.

Author information

1
Emory Vaccine Center, Emory University, Atlanta, GA 30329, USA; Yerkes National Primate Center, Emory University, Atlanta, GA 30329, USA.
2
Center for Inflammation, Immunity, and Infection, Georgia State University, Atlanta, GA 30302, USA.
3
Center for Inflammation, Immunity, and Infection, Georgia State University, Atlanta, GA 30302, USA; INSERM U1107, Universite d'Auvergne, 63001 Clermont-Ferrand Cedex 1, France.
4
National Gnotobiotic Rodent Resource Center, University of North Carolina, Chapel Hill, NC 27514, USA.
5
Yerkes National Primate Center, Emory University, Atlanta, GA 30329, USA.
6
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.
7
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
8
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.

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.

PMID:
25220212
PMCID:
PMC4169736
DOI:
10.1016/j.immuni.2014.08.009
[Indexed for MEDLINE]
Free PMC Article

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