当前位置: X-MOL 学术Mol. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Regulation of key molecules of immunological synapse by T11TS immunotherapy abrogates Cryptococcus neoformans infection in rats.
Molecular Immunology ( IF 3.6 ) Pub Date : 2020-05-07 , DOI: 10.1016/j.molimm.2020.04.021
Omar Faruk Sk Md 1 , Iman Hazra 2 , Ankur Datta 2 , Somnath Mondal 2 , Saibal Moitra 2 , Suhnrita Chaudhuri 3 , Prasanta Kumar Das 2 , Anjan Kumar Basu 4 , Roshnara Mishra 5 , Swapna Chaudhuri 2
Affiliation  

Cryptococcus neoformans infects and disseminates in hosts with diminished T cell responses. The immunomodulator T11TS (T11 target structure) had profound potential in glioma as well as C. neoformans infected model for disease amelioration. It is been established by our group that T11TS potentiates Calcineurin-NFAT pathway in T cells of C. neoformans infected rats. We investigated the upstream Immunological Synapse (IS) molecules that are vital for the foundation of initial signals for downstream signaling, differentiation and proliferation in T cells. Improved RANTES level in the T11TS treated groups suggests potential recruitment of T cells. Down-regulation of TCRαβ, CD3ζ, CD2, CD45 and CD28 molecules by cryptococcus were boosted after T11TS therapy. Heightened expression of inhibitory molecule CTLA-4 in cryptococcosis was dampened by T11TS. The decline of MHC I, MHC II and CD80 expression on macrophages by C. neoformans were enhanced by T11TS. The dampening of positive regulators and upsurge of negative regulators of the IS during cryptococcosis was reversed with T11TS therapy resulting in enhanced clearance of fungus from the lungs as envisaged by our histological studies. This preclinical study with T11TS opens a new prospect for potential immunotherapeutic intervention against the devastating C. neoformans infection with positive aspect for the long-term solution and a safer immunotherapeutic regimen.

中文翻译:

T11TS免疫疗法对免疫突触关键分子的调节可消除大鼠新隐球菌感染。

新型隐球菌感染并在T细胞反应减弱的宿主中传播。免疫调节剂T11TS(T11靶结构)在神经胶质瘤以及新福寿杆菌感染的疾病缓解模型中具有深远的潜力。我们的研究小组确定,T11TS可以增强感染新孢子虫的大鼠T细胞中的钙调神经磷酸酶-NFAT途径。我们研究了上游免疫突触(IS)分子,这些分子对于T细胞中下游信号传导,分化和增殖的初始信号的基础至关重要。T11TS治疗组的RANTES水平提高,提示潜在的T细胞募集。T11TS治疗后,隐球菌可增强TCRαβ,CD3ζ,CD2,CD45和CD28分子的下调。T11TS抑制了隐球菌病中抑制分子CTLA-4的表达增加。T11TS增强了新孢梭菌在巨噬细胞上MHC I,MHC II和CD80表达的下降。T11TS治疗可逆转隐球菌病期间IS的正调节剂的减弱和IS负调节剂的升高,从而如我们的组织学研究所设想的那样,导致真菌从肺部清除的增强。这项针对T11TS的临床前研究为潜在的针对毁灭性新孢子虫感染的潜在免疫治疗干预开辟了新的前景,从长远来看,它具有长期解决方案和更安全的免疫治疗方案。T11TS治疗可逆转隐球菌病期间IS的正调节剂的减弱和IS负调节剂的升高,从而如我们的组织学研究所设想的那样,导致真菌从肺部清除的增强。这项针对T11TS的临床前研究为潜在的针对毁灭性新孢子虫感染的潜在免疫治疗干预开辟了新的前景,从长远角度来看,该解决方案具有积极意义,并且免疫治疗方案更安全。T11TS治疗可逆转隐球菌病期间IS的正调节剂的减弱和IS负调节剂的升高,从而如我们的组织学研究所设想的那样,导致真菌从肺部清除的增强。这项针对T11TS的临床前研究为潜在的针对毁灭性新孢子虫感染的潜在免疫治疗干预开辟了新的前景,从长远角度来看,该解决方案具有积极意义,并且免疫治疗方案更安全。
更新日期:2020-05-07
down
wechat
bug