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

Jason Z. Oh, Rajesh Ravindran, Benoit Chassaing, Frederic A. Carvalho, Mohan S. Maddur, Maureen Bower, Paul Hakimpour, Kiran P. Gill, Helder I. Nakaya, Felix Yarovinsky, R. Balfour Sartor, Andrew T. Gewirtz, Bali Pulendran

Research output: Contribution to journalArticlepeer-review

263 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)478-492
Number of pages15
JournalImmunity
Volume41
Issue number3
DOIs
StatePublished - Sep 18 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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