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人类淋巴丝虫马来布鲁线虫的交叉反应分子可抑制杜氏利什曼原虫在仓鼠体内的感染。

Cross reactive molecules of human lymphatic filaria Brugia malayi inhibit Leishmania donovani infection in hamsters.

作者信息

Verma Richa, Joseph Sujith K, Kushwaha Vikas, Kumar Vikash, Siddiqi M I, Vishwakarma Preeti, Shivahare Rahul, Gupta Suman, Murthy P K

机构信息

Division of Parasitology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Extension, Lucknow 226031, India.

Molecular and Structural Biology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Vistar, Lucknow 226 031, India.

出版信息

Acta Trop. 2015 Dec;152:103-111. doi: 10.1016/j.actatropica.2015.08.018. Epub 2015 Sep 1.

Abstract

Coinfections are common in natural populations and the outcome of their interactions depends on the immune responses of the host elicited by the parasites. Earlier we showed that immunization with BmAFII (Sephadex G-200 eluted) fraction of human lymphatic filaria Brugia malayi inhibited progression of Leishmania donovani infection in golden hamsters. In the present study we identified cross reactive molecules of B. malayi, and investigated their effect on L. donovani infection and associated immune responses in the host. The sequence alignment and sharing of linear T- and B-cell epitopes in protein molecules of B. malayi and L. donovani counterparts were studied in silico. Hamsters were immunized with robustly cross reactive SDS-PAGE resolved fractions F6 (54.2-67.8kDa) and F9 (41.3-45.0kDa) of B. malayi and subsequently inoculated with amastigotes of L. donovani intracardially. F6 inhibited (∼72%) L. donovani infection and upregulated Th1 cytokine expression, lymphoproliferation, IgG2, IgG2/3 levels and NO production, and downregulated Th2 cytokine expression. Sequences in HSP60 and EF-2 of F6 and L. donovani counterparts were conserved and B- and T-cell epitopes in the proteins shared antigenic regions. In conclusion, leishmania-cross reactive molecules of filarial parasite considerably inhibited leishmanial infection via Th1-mediated immune responses and NO production. Common B- and T-cell epitope regions in HSP60 and EF-2 of the parasites might have contributed to the inhibitory effect on the L. donovani infection. Thus, leishmania-cross reactive filarial parasite molecules may help in designing prophylactic(s) against L. donovani.

摘要

共感染在自然种群中很常见,它们相互作用的结果取决于寄生虫引发的宿主免疫反应。此前我们发现,用马来布鲁线虫(Brugia malayi)的BmAFII(Sephadex G - 200洗脱)组分免疫可抑制金黄仓鼠中杜氏利什曼原虫(Leishmania donovani)感染的进展。在本研究中,我们鉴定了马来布鲁线虫的交叉反应分子,并研究了它们对杜氏利什曼原虫感染及宿主相关免疫反应的影响。通过计算机模拟研究了马来布鲁线虫和杜氏利什曼原虫对应蛋白分子中线性T细胞和B细胞表位的序列比对和共享情况。用马来布鲁线虫具有强交叉反应性的SDS - PAGE分离组分F6(54.2 - 67.8kDa)和F9(41.3 - 45.0kDa)免疫仓鼠,随后经心内接种杜氏利什曼原虫无鞭毛体。F6抑制了(约72%)杜氏利什曼原虫感染,上调了Th1细胞因子表达、淋巴细胞增殖、IgG2、IgG2/3水平和一氧化氮生成,并下调了Th2细胞因子表达。F6和杜氏利什曼原虫对应物的热休克蛋白60(HSP60)和延伸因子2(EF - 2)中的序列保守,蛋白质中的B细胞和T细胞表位共享抗原区域。总之,丝虫寄生虫的利什曼原虫交叉反应分子通过Th1介导的免疫反应和一氧化氮生成显著抑制了利什曼原虫感染。寄生虫HSP60和EF - 2中常见的B细胞和T细胞表位区域可能对杜氏利什曼原虫感染的抑制作用有贡献。因此,利什曼原虫交叉反应的丝虫寄生虫分子可能有助于设计针对杜氏利什曼原虫的预防措施。

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