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

TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination.
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TLR5介导的肠道微生物群的感觉是对季节性流感疫苗接种的抗体反应所必需的。

DOI:
10.1016/j.immuni.2014.08.009
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发表时间:
2014-09-18
期刊:
影响因子:
32.4
通讯作者:
Pulendran, Bali
Pulendran, Bali
中科院分区:
医学1区
文献类型:
--
作者:
Oh, Jason Z.;Ravindran, Rajesh;Chassaing, Benoit;Carvalho, Frederic A.;Maddur, Mohan S.;Bower, Maureen;Hakimpour, Paul;Gill, Kiran P.;Nakaya, Helder I.;Yarovinsky, Felix;Sartor, R. Balfour;Gewirtz, Andrew T.;Pulendran, Bali

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人体对三价灭活流感疫苗(TIV)的免疫力的系统生物学分析揭示了TLR 5的早期表达与抗体应答幅度之间的相关性。接种Trl 5 −/−小鼠导致抗体滴度降低和浆细胞频率降低,证明了TLR 5在对TIV的免疫中的作用。这是由于未能感知宿主微生物群。因此,在无菌或驱虫处理的小鼠中,抗体反应受到损害,但通过用有鞭毛但无鞭毛的E.杆菌TLR 5介导的鞭毛蛋白感应直接促进浆细胞分化,并通过刺激淋巴结巨噬细胞产生浆细胞生长因子。最后,TLR 5介导的微生物群传感也影响了灭活脊髓灰质炎疫苗的抗体应答,但对佐剂疫苗或减毒黄热病活疫苗没有影响。这些结果揭示了肠道微生物群在促进对疫苗接种的免疫力方面的未被重视的作用。
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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