Search

Schistosomiasis is a significant public health problem in sub-Saharan Africa, China, Southeast Asia, and regions of South and Central America affecting about 189 million people. Kunitz-type serine protease inhibitors have been identified as important players in the interaction of other flatworm parasites with their mammalian hosts. They are involved in host blood coagulation, fibrinolysis, inflammation, and ion channel blocking, all of them critical biological processes, which make them interesting targets to develop a vaccine. Here, we evaluate the protective efficacy of chemically synthesized T- and B-cell peptide epitopes derived from a kunitz protein from Schistosoma mansoni. Putative kunitz-type protease inhibitor proteins were identified in the S. mansoni genome, and their expression was analyzed by RNA-seq. Gene expression analyses showed that the kunitz protein Smp_147730 (Syn. Smp_311670) was dramatically and significantly up-regulated in schistosomula and adult worms when compared to the invading cercariae. T- and B-cell epitopes were predicted using bioinformatics tools, chemically synthesized, and formulated in the Adjuvant Adaptation (ADAD) vaccination system. BALB/c mice were vaccinated and challenged with S. mansoni cercariae. Kunitz peptides were highly protective in vaccinated BALB/c mice showing significant reductions in recovery of adult females (89–91%) and in the numbers of eggs trapped in the livers (77–81%) and guts (57–77%) of mice. Moreover, liver lesions were significantly reduced in vaccinated mice (64–65%) compared to infected control mice. The vaccination regime was well-tolerated with both peptides. We propose the use of these peptides, alone or in combination, as reliable candidates for vaccination against schistosomiasis. © Copyright © 2019 Hernández-Goenaga, López-Abán, Protasio, Vicente Santiago, del Olmo, Vanegas, Fernández-Soto, Patarroyo and Muro.

各種の悪性腫瘍で増加する糖鎖であるsialyl Lewis X（SLEX）が正常リンパ組織、末梢血や皮膚においてどのような発現をしているのかを免疫組織化学やフローサイトメトリーにて検索した。SLEXは末梢血のリンパ球において、NK細胞やT細胞の一部に発現していた。リンパ節では傍皮質やリンパ洞の一部の組織球に発現しており、特に皮膚病性リンパ節炎ではS100陽性の樹状細胞（Langerhans細胞）の一部にSLEXが陽性であった。また、皮膚表皮でもCD1a陽性Langerhans細胞の一部がSLEX陽性であった。以上の所見から、従来指摘されていた表皮の抗原提示細胞であるLangerhans細胞のリンパ節への移行が確認された。更にこのLangerhans細胞移行の機序には内皮細胞E-selectinとLangerhans細胞SLEXの相互反応が関与する可能性が示唆された。Tissue distribution of sialyl Lewis X（SLEX） in the lymphoid tissues and peripheral blood lymphocytes was studied by immunohistochemistry and flow cytometry. SLEX was expressed in the subpopulation of T cells and natural killer cells of peripheral blood and histiocytes of paracortical areas of lymph nodes. In the dermatopathic lymphadenopathy, some S100+dendritic cells of the paracortical area were positive for SLEX. A subpopulation of CD1a-positiveepidermal dendritic cells expressed SLEX. These results showed that SLEX was ex-pressed in a subpopulation of Langerhans cells, which are antigen-presenting cells to T-cells. The migration of Langerhans cells from skin to lymph nodes is thought to be performed via the interaction of SLEX of Langerhans cells and E-selectin of the endothelial cells.

Human CD1 antigens have a similar tissue distribution and overall structure to (mouse) TL. However recent data from human CD1 suggest that the mouse homologue is not TL. Since no human TL has been conclusively demonstrated, we have analysed the murine CD1 genes. Two closely linked genes are found in a tail to tail orientation and the limited polymorphism found shows that, as in humans, the CD1 genes are not linked to the MHC. Both genes are found to be equally transcribed in the thymus, but differentially in other cell types. The expression in liver, especially, does not parallel CD1 in humans. This demonstrates conclusively that CD1 and TL are distinct and can co-exist in the same thymus. It is paradoxical that despite the structural similarity between mouse and human CD1, the tissue distribution of human CD1 is closer to TL. The possibility of a functional convergence between MHC molecules and CD1 is discussed.