@article{0f71fe28dfda4a698c42ba3880cb27c0,
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.",
author = "Oh, {Jason Z.} and Rajesh Ravindran and Benoit Chassaing and Carvalho, {Frederic A.} and Maddur, {Mohan S.} and Maureen Bower and Paul Hakimpour and Gill, {Kiran P.} and Nakaya, {Helder I.} and Felix Yarovinsky and Sartor, {R. Balfour} and Gewirtz, {Andrew T.} and Bali Pulendran",
note = "Funding Information: We thank A. Darfeuille-Michaud for providing LF82 strains; R.L. Toennisson and M. Bower for technical assistance with gnotobiotic studies; and B. Cervasi for macrophage and B cell sorting. This work was supported by NIH grants HHSN272201400004C, U19AI090023, U54AI057157, R37AI48638, R37DK057665, U19AI057266, and AI100663-02 (to B.P.) and a grant from the Bill and Melinda Gates Foundation (to B.P.). Additional support was provided by grants from the NIH (DK099071 and DK083890) (A.T.G.), Research Fellowship award from the Crohn{\textquoteright}s and Colitis Foundation of America (B.C.), NIH (AI085263) and the Burroughs Wellcome Fund (F.Y.), NIH (P40 OD010995, P30 DK34987) and Crohn{\textquoteright}s and Colitis Foundation of America (R.B.S., NGRRC), and Research Fellowship award from the Influenza Pathogenesis and Immunology Research Center – CEIRS (J.Z.O.). Publisher Copyright: {\textcopyright} 2014 Elsevier Inc.",
year = "2014",
month = sep,
day = "18",
doi = "10.1016/j.immuni.2014.08.009",
language = "English (US)",
volume = "41",
pages = "478--492",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "3",
}