TLR5-mediated Sensing of Gut Microbiota is Necessary for Antibody Responses to Seasonal Influenza Vaccination

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2014 Sep 16

PMID 25220212

Citations 288

Authors

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

Affiliations

Soon will be listed here.

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.

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