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Paper of the Month September 2014

TLR5-Mediated Sensing of Gut Microbiota Is Necessary for Antibody Responses to Seasonal InfluenzaVaccination

Immunity. 2014 Sep 18;41(3):478-92. doi: 10.1016/j.immuni.2014.08.009. Epub 2014 Sep 11.


Oh JZ1, Ravindran R1, Chassaing B2, Carvalho FA3, Maddur MS1, Bower M4, Hakimpour P5, Gill KP1, Nakaya HI6, Yarovinsky F7, Sartor RB4, Gewirtz AT2,Pulendran B8.


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.