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基于转唾液酸酶的候选疫苗可预防感染,不仅能诱导效应性免疫反应,还能影响具有调节/抑制表型的细胞。

Trans-sialidase-based vaccine candidate protects against infection, not only inducing an effector immune response but also affecting cells with regulatory/suppressor phenotype.

作者信息

Prochetto Estefanía, Roldán Carolina, Bontempi Iván A, Bertona Daiana, Peverengo Luz, Vicco Miguel H, Rodeles Luz M, Pérez Ana R, Marcipar Iván S, Cabrera Gabriel

机构信息

Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.

Facultad de Ciencias Médicas, Universidad Nacional del Litoral, Santa Fe, Argentina.

出版信息

Oncotarget. 2017 May 25;8(35):58003-58020. doi: 10.18632/oncotarget.18217. eCollection 2017 Aug 29.

Abstract

Prophylactic and/or therapeutic vaccines have an important potential to control ()infection. The involvement of regulatory/suppressor immune cells after an immunization treatment and infection has never been addressed. Here we show that a new trans-sialidase-based immunogen (TSf) was able to confer protection, correlating not only with beneficial changes in effector immune parameters, but also influencing populations of cells related to immune control. Regarding the effector response, mice immunized with TSf showed a TS-specific antibody response, significant delayed-type hypersensitivity (DTH) reactivity and increased production of IFN-γ by CD8+ splenocytes. After a challenge with , TSf-immunized mice showed 90% survival and low parasitemia as compared with 40% survival and high parasitemia in PBS-immunized mice. In relation to the regulatory/suppressor arm of the immune system, after infection TSf-immunized mice showed an increase in spleen CD4+ Foxp3+ regulatory T cells (Treg) as compared to PBS-inoculated and infected mice. Moreover, although infection elicited a notable increase in myeloid derived suppressor cells (MDSC) in the spleen of PBS-inoculated mice, TSf-immunized mice showed a significantly lower increase of MDSC. Results presented herein highlight the need of studying the immune response as a whole when a vaccine candidate is rationally tested.

摘要

预防性和/或治疗性疫苗在控制()感染方面具有重要潜力。免疫治疗和感染后调节性/抑制性免疫细胞的参与情况从未得到研究。在此我们表明,一种基于新型转唾液酸酶的免疫原(TSf)能够提供保护,这不仅与效应免疫参数的有益变化相关,还影响与免疫控制相关的细胞群体。关于效应反应,用TSf免疫的小鼠表现出TS特异性抗体反应、显著的迟发型超敏反应(DTH)反应性以及CD8 +脾细胞产生IFN-γ增加。在用()攻击后,与用PBS免疫的小鼠40%的存活率和高寄生虫血症相比,用TSf免疫的小鼠显示出90%的存活率和低寄生虫血症。关于免疫系统的调节/抑制分支,在感染()后,与接种PBS并感染的小鼠相比,用TSf免疫的小鼠脾脏中CD4 + Foxp3 +调节性T细胞(Treg)增加。此外,尽管感染在接种PBS的小鼠脾脏中引起髓源性抑制细胞(MDSC)显著增加,但用TSf免疫的小鼠MDSC的增加明显较低。本文给出的结果突出了在合理测试候选疫苗时对整体免疫反应进行研究的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2575/5601629/ab4e0fc31955/oncotarget-08-58003-g001.jpg

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