IκBζ facilitates protective immunity against Salmonella infection via Th1 differentiation and IgG production
IκBζ facilitates protective immunity against Salmonella infection via Th1 differentiation and IgG production
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DOI：
10.1038/s41598-019-44019-3
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发表时间：
2019-06-10
影响因子：
4.6
通讯作者：
Ko, Hyun-Jeong
中科院分区：
文献类型：
--
作者：
Ahn, Jae-Hee;Cho, Jaewon;Ko, Hyun-Jeong
通过TLR配体和IL-1的刺激快速诱导κ B（I κ，B）-ζ转录的抑制剂。尽管I κ B zeta在炎症部位有高表达，但I κ B zeta与宿主通过针对细菌感染的全身免疫应答进行防御的关联仍不清楚。口服免疫重组减毒沙门氏菌疫苗（RASV）菌株没有保护I κ B ζ缺陷小鼠免受致命的沙门氏菌攻击。I κ B ζ缺陷小鼠不能产生沙门氏菌LPS特异性IgG，尤其是IgG 2a，尽管口服RASV后炎性细胞因子产生和免疫细胞浸润到肝脏中增加。此外，尽管I kappa B zeta缺陷型B细胞具有内在抗体类别转换缺陷，但I kappa B zeta缺陷型小鼠表现出增强的脾脏生发中心反应，随后总IgG产量增加。I κ B ζ缺陷型CD 4（+）T细胞分化为Th 1细胞的能力较差。在体外用热灭活的RASV再刺激后，来自用RASV免疫的I κ B ζ缺陷小鼠的CD 4（+）T细胞产生的IFN-γ显著降低，表明I κ B ζ缺陷小鼠由于Th 1和IgG产生不足而未能建立针对沙门氏菌感染的保护性免疫应答。因此，I κ B zeta通过诱导Th 1分化随后产生IgG在保护免受沙门氏菌感染中是至关重要的。
Inhibitor of kappa B (I kappa,B)-zeta transcription is rapidly induced by stimulation with TLR ligands and IL-1. Despite high I kappa B zeta expression in inflammation sites, the association of I kappa B zeta with host defence via systemic immune responses against bacterial infection remains unclear. Oral immunisation with a recombinant attenuated Salmonella vaccine (RASV) strain did not protect I kappa B zeta-deficient mice against a lethal Salmonella challenge. I kappa B zeta-deficient mice failed to produce Salmonella LPS-specific IgG, especially IgG2a, although inflammatory cytokine production and immune cell infiltration into the liver increased after oral RASV administration. Moreover, I kappa B zeta-deficient mice exhibited enhanced splenic germinal centre reactions followed by increased total IgG production, despite I kappa B zeta-deficient B cells having an intrinsic antibody class switching defect. I kappa B zeta-deficient CD4(+) T cells poorly differentiated into Th1 cells. IFN-gamma production by CD4(+) T cells from I kappa B zeta -deficient mice immunised with RASV significantly decreased after restimulation with heat-killed RASV in vitro, suggesting that I kappa B zeta-deficient mice failed to mount protective immune responses against Salmonella infection because of insufficient Th1 and IgG production. Therefore, I kappa B zeta is crucial in protecting against Salmonella infection by inducing Th1 differentiation followed by IgG production.