关键词: Immunomodulation Leishmania Macrophages Swarna Bhasma T cells

Mesh : Arsenic Drug Combinations Gold / administration & dosage pharmacology Latex / administration & dosage pharmacology Lead Calotropis Medicine, Ayurvedic Macrophages / drug effects immunology CD4-Positive T-Lymphocytes / immunology Phagocytes / drug effects immunology Leishmaniasis / immunology parasitology Leishmania donovani / drug effects growth & development immunology Antigens, Protozoan / immunology Antigen Presentation Th1 Cells / immunology Animals Mice RAW 264.7 Cells Female Mice, Inbred BALB C

来  源:   DOI:10.1007/s12011-023-03659-3   PDF(Pubmed)

Abstract:
In leishmaniasis, the protective immunity is largely mediated by proinflammatory cytokine producing abilities of T cells and an efficient parasite killing by phagocytic cells. Notwithstanding a substantial progress that has been made during last decades, the mechanisms or factors involved in establishing protective immunity against Leishmania are not identified. In ancient Indian literature, metallic \"bhasma,\" particularly that of \"swarna\" or gold (fine gold particles), is indicated as one of the most prominent metal-based therapeutic medicine, which is known to impart protective and curative properties in various health issues. In this work, we elucidated the potential of swarna bhasma (SB) on the effector properties of phagocytes and antigen-activated CD4+ T cells in augmenting the immunogenicity of L. donovani antigens. The characterization of SB revealing its shape, size, composition, and measurement of cytotoxicity established the physiochemical potential for its utilization as an immunomodulator. The activation of macrophages with SB enhanced their capacity to produce nitric oxide and proinflammatory cytokines, which eventually resulted in reduced uptake of parasites and their proliferation in infected cells. Further, in Leishmania-infected animals, SB administration reduced the generation of IL-10, an anti-inflammatory cytokine, and enhanced pro-inflammatory cytokine generation by antigen activated CD4+ T cells with increased frequency of double (IFNγ+/TNFα+) and triple (IFNγ+TNFα+IL-2+) positive cells and abrogated disease pathogeneses at the early days of infection. Our results also suggested that cow-ghee (A2) emulsified preparation of SB, either alone or with yashtimadhu, a known natural immune modulator which enhances the SB\'s potential in enhancing the immunogenicity of parasitic antigens. These findings suggested a definite potential of SB in enhancing the effector functions of phagocytes and CD4+ T cells against L. donovani antigens. Therefore, more studies are needed to elucidate the mechanistic details of SB and its potential in enhancing vaccine-induced immunity.
摘要:
在利什曼病中,保护性免疫主要由T细胞产生促炎细胞因子的能力和吞噬细胞对寄生虫的有效杀伤介导。尽管在过去几十年中取得了实质性进展,尚未确定建立针对利什曼原虫的保护性免疫的机制或因素。在古代印度文学中,金属\“bhasma,\"特别是\"swarna\"或黄金(精细的黄金颗粒),被认为是最突出的基于金属的治疗药物之一,已知在各种健康问题中具有保护性和治疗性。在这项工作中,我们阐明了swarnabhasma(SB)对吞噬细胞和抗原激活的CD4T细胞的效应子特性的潜力,以增强唐氏乳杆菌抗原的免疫原性。SB的特征揭示了它的形状,尺寸,composition,和细胞毒性的测量建立了其用作免疫调节剂的物理化学潜力。具有SB的巨噬细胞的活化增强了它们产生一氧化氮和促炎细胞因子的能力,这最终导致寄生虫的摄取减少和它们在感染细胞中的增殖。Further,在利什曼原虫感染的动物中,SB给药减少了IL-10的产生,IL-10是一种抗炎细胞因子,抗原激活的CD4T细胞增强了促炎细胞因子的产生,双(IFNγ/TNFα)和三(IFNγTNFαIL-2)阳性细胞的频率增加,并在感染早期消除了疾病的发病机制。我们的结果还表明,牛酥油(A2)乳化制剂的SB,无论是单独还是与yashtimadhu,一种已知的天然免疫调节剂,可增强SB在增强寄生虫抗原免疫原性方面的潜力。这些发现表明,SB在增强吞噬细胞和CD4T细胞针对donovani乳杆菌抗原的效应子功能方面具有明确的潜力。因此,需要更多的研究来阐明SB的机制细节及其在增强疫苗诱导免疫方面的潜力.
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