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

TitleTLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination.
Publication TypeJournal Article
Year of Publication2014
AuthorsOh JZ, Ravindran R, Chassaing B, Carvalho FA, Maddur MS, Bower M, Hakimpour P, Gill KP, Nakaya HI, Yarovinsky F, R Sartor B, Gewirtz AT, Pulendran B
JournalImmunity
Volume41
Issue3
Pagination478-92
Date Published09/18/2014
ISSN1097-4180
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.

DOI10.1016/j.immuni.2014.08.009
Alternate JournalImmunity
PubMed ID25220212
PubMed Central IDPMC4169736
Grant ListAI085263 / AI / NIAID NIH HHS / United States
AI100663-02 / AI / NIAID NIH HHS / United States
DK083890 / DK / NIDDK NIH HHS / United States
DK099071 / DK / NIDDK NIH HHS / United States
HHSN272201400004C / / PHS HHS / United States
P30 DK34987 / DK / NIDDK NIH HHS / United States
P40 OD010995 / OD / NIH HHS / United States
R37 AI048638 / AI / NIAID NIH HHS / United States
R37 DK057665 / DK / NIDDK NIH HHS / United States
R37AI48638 / AI / NIAID NIH HHS / United States
R37DK057665 / DK / NIDDK NIH HHS / United States
U19 AI057266 / AI / NIAID NIH HHS / United States
U19 AI090023 / AI / NIAID NIH HHS / United States
U19AI057266 / AI / NIAID NIH HHS / United States
U19AI090023 / AI / NIAID NIH HHS / United States
U54AI057157 / AI / NIAID NIH HHS / United States
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