Verma Richa, Kushwaha Vikas, Pandey Smriti, Thota Jagadeshwar Reddy, Vishwakarma Preeti, Parmar Naveen, Yadav Pawan Kumar, Tewari Prachi, Kar Susanta, Shukla Praveen Kumar, Murthy Puvvada Kalpana
Division of Parasitology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, Uttar Pradesh, 226031, India.
Division of Microbiology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, Uttar Pradesh, 226031, India.
Parasitol Res. 2018 Sep;117(9):2901-2912. doi: 10.1007/s00436-018-5981-9. Epub 2018 Jun 26.
We earlier found that F6 fraction of human filaria Brugia malayi cross-reacted with sera of Leishmania donovani infected hamsters and immunization with F6 inhibited both filarial and leishmanial infections. In the present study, we identified a 52.9-93.6 kDa fraction (Ld1) of L. donovani that cross-reacted with sera of B. malayi infected animals and investigated effect of Ld1 on filarial infection. Immunization of BALB/c mice with Ld1 facilitated B. malayi infection with remarkable increase in parasite burden. Facilitation of filarial infection was associated with downregulated cell proliferation, IL-5, IL-13, IFN-γ, TNF-α, and IL-2 levels and upregulated IL-4 and TGF-β. Ld1 exposure also suppressed MHC class-I, MHC class-II, and FcεR1 expression, and phagocytosis in naive mouse macrophages, and CD4+, CD8+, and CD19+ cell population in mouse spleen. Two-dimensional electrophoresis and matrix-assisted laser desorption ionization-time of flight-mass spectrometry revealed eight proteins in Ld1: putative heat shock protein (HSP) 70-related protein 1, HSP70 mitochondrial precursor, alanine aminotransferase, 2,3-bisphosphoglycerate-independent phosphoglycerate mutase, protein disulfide isomerase, putative ATPase beta subunit, trypanothione reductase, and a hypothetical protein. HSP70 protein mitochondrial precursor and trypanothione reductase showed homology with Trypanosoma cruzi and L. donovani, respectively, and the rest 6 proteins including hypothetical protein bear homology with L. infantum. In conclusion, the present study for the first time shows that immunization with filarial cross-reactive Ld1 fraction of L. donovani facilitates filarial infection by modulating Th1 and Th2 responses. Ld1 molecules may therefore facilitate filarial infection in filaria-leishmania co-infection.
我们先前发现,马来布鲁线虫的F6组分与杜氏利什曼原虫感染的仓鼠血清发生交叉反应,用F6免疫可抑制丝虫和利什曼原虫感染。在本研究中,我们鉴定出杜氏利什曼原虫的一个52.9 - 93.6 kDa组分(Ld1),它与马来布鲁线虫感染动物的血清发生交叉反应,并研究了Ld1对丝虫感染的影响。用Ld1免疫BALB/c小鼠促进了马来布鲁线虫感染,寄生虫负荷显著增加。丝虫感染的促进与细胞增殖、IL-5、IL-13、IFN-γ、TNF-α和IL-2水平下调以及IL-4和TGF-β上调有关。Ld1暴露还抑制了未感染小鼠巨噬细胞中的MHC I类、MHC II类和FcεR1表达以及吞噬作用,以及小鼠脾脏中的CD4 +、CD8 +和CD19 +细胞群体。二维电泳和基质辅助激光解吸电离飞行时间质谱分析显示Ld1中有8种蛋白质:假定的热休克蛋白(HSP)70相关蛋白1、HSP70线粒体前体、丙氨酸转氨酶、非2,3-二磷酸甘油酸依赖的磷酸甘油酸变位酶、蛋白质二硫键异构酶、假定的ATP酶β亚基、锥虫硫醇还原酶和一种假定蛋白。HSP70蛋白线粒体前体和锥虫硫醇还原酶分别与克氏锥虫和杜氏利什曼原虫具有同源性,其余6种蛋白包括假定蛋白与婴儿利什曼原虫具有同源性。总之,本研究首次表明,用杜氏利什曼原虫的丝虫交叉反应性Ld1组分免疫可通过调节Th1和Th2反应促进丝虫感染。因此,Ld1分子可能在丝虫 - 利什曼原虫共感染中促进丝虫感染。