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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 Pulendranemail
DOI: http://dx.doi.org/10.1016/j.immuni.2014.08.009
Publication stage: In Press Corrected Proof
Summary
To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect.
Highlights
?Report on the impact of microbiome on vaccine immunity
?Example of a novel insight obtained from a systems vaccinology study in human
?New role for microbiome on modulating short- and long-lived plasma cell responses
?New insight on the regulation of immunity to influenza vaccine
Summary
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.
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 Pulendranemail
DOI: http://dx.doi.org/10.1016/j.immuni.2014.08.009
Publication stage: In Press Corrected Proof
Summary
To view the full text, please login as a subscribed user or purchase a subscription. Click here to view the full text on ScienceDirect.
Highlights
?Report on the impact of microbiome on vaccine immunity
?Example of a novel insight obtained from a systems vaccinology study in human
?New role for microbiome on modulating short- and long-lived plasma cell responses
?New insight on the regulation of immunity to influenza vaccine
Summary
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.
