Composition of the Schistosoma mansoni worm secretome: Identification of immune modulatory Cyclophilin A.
Composition of the Schistosoma mansoni worm secretome: Identification of immune modulatory Cyclophilin A.
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DOI：
10.1371/journal.pntd.0006012
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发表时间：
2017-10
影响因子：
3.8
通讯作者：
Fallon PG
中科院分区：
文献类型：
--
作者：
Floudas A;Cluxton CD;Fahel J;Khan AR;Saunders SP;Amu S;Alcami A;Fallon PG
曼氏血吸虫蠕虫通过产生排泄/分泌分子来调节感染宿主的免疫系统以促进其自身的存活，所述排泄/分泌分子与宿主的多种细胞类型（包括免疫系统的细胞类型）相互作用。在此，我们对S. Mansoni成虫雄虫分泌蛋白组，鉴定了111个蛋白，包括7个候选疫苗和几个具有潜在免疫调节活性的分子。在分泌组中存在的分子中，鉴定出类似于人亲环素A的17- 19 kDa蛋白。鉴于亲环素A通过调节抗原呈递细胞活性来调节免疫系统的能力，我们试图确定重组S。mansoni亲环素A（rSmCypA）能够在体外条件下调节骨髓来源的树突状细胞（BMDC）和T细胞应答。rSmCypA具有酶活性，能够改变LPS激活的树突状细胞的促炎细胞因子谱。rSmCypA还调节DC在诱导CD 4 + T细胞增殖中的功能，具有Treg细胞的优先扩增。这项工作证明了S.曼氏血吸虫雄虫分泌体和免疫调节活性。曼氏亲环素A蠕虫以其改变宿主免疫反应以促进其生存的能力而闻名。一种这样的机制是蠕虫分泌具有免疫调节活性的分子的倾向;这些分子改变宿主免疫的各个方面以使寄生虫受益。分泌组的详细表征后，我们已经确定，亲环素A分泌的成人曼氏血吸虫和蛋白质有能力改变树突状细胞和T细胞功能在体外诱导T细胞的调节表型。
The helminth Schistosoma mansoni modulates the infected host’s immune system to facilitate its own survival, by producing excretory/secretory molecules that interact with a variety of the host’s cell types including those of the immune system. Herein, we characterise the S. mansoni adult male worm secretome and identify 111 proteins, including 7 vaccine candidates and several molecules with potential immunomodulatory activity. Amongst the molecules present in the secretome, a 17-19kDa protein analogous to human cyclophilin A was identified. Given the ability of cyclophilin A to modulate the immune system by regulating antigen presenting cell activity, we sought to determine whether recombinant S. mansoni Cyclophilin A (rSmCypA) is capable of modulating bone-marrow derived dendritic cell (BMDC) and T cell responses under in vitro conditions. rSmCypA was enzymatically active and able to alter the pro-inflammatory cytokine profile of LPS-activated dendritic cells. rSmCypA also modulated DC function in the induction of CD4+ T cell proliferation with a preferential expansion of Treg cells. This work demonstrates the unique protein composition of the S. mansoni male worm secretome and immunomodulatory activity of S. mansoni Cyclophilin A. Helminths are known for their ability to alter the host’s immune response in order to promote their survival. One such mechanism is the propensity of helminths to secrete molecules with immunomodulatory activity; such molecules alter various aspects of host immunity to the benefit of the parasite. Following detailed characterisation of the secretome, we have identified that Cyclophilin A is secreted from adult Schistosoma mansoni and that the protein has the capacity to alter dendritic cell and T cell function in vitro by inducing a T cell regulatory phenotype.
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影响因子：
1.5
作者：
Hewitson, James P.;Grainger, John R.;Maizels, Rick M.
通讯作者：
Maizels, Rick M.
DOI：
10.1084/jem.20101074
发表时间：
2010-10-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Grainger JR;Smith KA;Hewitson JP;McSorley HJ;Harcus Y;Filbey KJ;Finney CA;Greenwood EJ;Knox DP;Wilson MS;Belkaid Y;Rudensky AY;Maizels RM
通讯作者：
Maizels RM
影响因子：
4.4
作者：
Kane, CM;Cervi, L;Pearce, EJ
通讯作者：
Pearce, EJ
影响因子：
32.4
作者：
Colgan, J;Asmal, M;Luban, J
通讯作者：
Luban, J
影响因子：
5.5
作者：
Dupré, L;Kremer, L;Locht, C
通讯作者：
Locht, C