Topical AuNPs-Cys-Sm29 gel modulates the course of lesion development in experimental cutaneous leishmaniasis.

IF 3.4 2区医学 Q1 PARASITOLOGY

PLoS Neglected Tropical Diseases Pub Date : 2025-09-22 eCollection Date: 2025-09-01 DOI:10.1371/journal.pntd.0013510

Sayonara de M Viana, Luciana Cardoso, Pedro B Borba, Lucas P Carvalho, Juvana Moreira, Fabio Mambelli, Sergio C Oliveira, Edgar M Carvalho, Camila I de Oliveira

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引用次数: 0

Abstract

The Sm29 antigen from Schistosoma mansoni has been shown to downregulate excessive inflammation associated with immune-mediated diseases. In contrast, cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is marked by an inflammatory response that, when uncontrolled, contributes to disease pathology. In this study, we evaluated the therapeutic potential of topical rSm29 in combination with meglumine antimoniate (Sbv) in experimental murine CL. First, rSm29 was functionalized onto spherical gold nanoparticles using a cysteamine linker (AuNPs-Cys-Sm29). Topical application of this formulation of rSm29 significantly decreased ear lesion thickness, and the combination of topical AuNPs-Cys-Sm29 plus intraperitoneal Sbv also significantly reduced ear lesion thickness, parasite load in the infection site, and the local inflammatory infiltrate when compared to mice treated with Sbv only. The production of IFN-γ, TNF, and IL-10 was reduced in the draining lymph node, as well as the total number of CD3+CD4+IFN+ and CD3+CD4+TNF+ T cells in the infection site. This study demonstrated that combination therapy with topical AuNPs-Cys-Sm29 + systemic Sbv reduced inflammation without compromising parasite clearance. These findings highlight the potential of AuNPs-Cys-Sm29 as a host-directed strategy in treating cutaneous leishmaniasis (CL).

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外用AuNPs-Cys-Sm29凝胶调节实验性皮肤利什曼病的病变发展过程。

来自曼氏血吸虫的Sm29抗原已被证明可以下调与免疫介导疾病相关的过度炎症。相反，由巴西利什曼原虫（Viannia）引起的皮肤利什曼病（CL）的特点是炎症反应，如果不加以控制，则会导致疾病病理。在这项研究中，我们评估了局部rSm29联合锑酸meg - umine （Sbv）对实验性小鼠CL的治疗潜力。首先，利用半胱胺连接剂（AuNPs-Cys-Sm29）将rSm29功能化到球形金纳米颗粒上。外用该剂型rSm29可显著降低耳部病变厚度，外用AuNPs-Cys-Sm29联合腹腔注射Sbv与单用Sbv相比，也可显著降低耳部病变厚度、感染部位寄生虫载量和局部炎症浸润。引流淋巴结中IFN-γ、TNF和IL-10的产生减少，感染部位CD3+CD4+IFN+和CD3+CD4+TNF+ T细胞总数减少。该研究表明，局部AuNPs-Cys-Sm29 +全身Sbv联合治疗可减少炎症，同时不影响寄生虫清除。这些发现突出了AuNPs-Cys-Sm29作为治疗皮肤利什曼病（CL）的宿主导向策略的潜力。

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来源期刊

PLoS Neglected Tropical Diseases PARASITOLOGY-TROPICAL MEDICINE

自引率

10.50%

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723

期刊介绍： PLOS Neglected Tropical Diseases publishes research devoted to the pathology, epidemiology, prevention, treatment and control of the neglected tropical diseases (NTDs), as well as relevant public policy. The NTDs are defined as a group of poverty-promoting chronic infectious diseases, which primarily occur in rural areas and poor urban areas of low-income and middle-income countries. Their impact on child health and development, pregnancy, and worker productivity, as well as their stigmatizing features limit economic stability. All aspects of these diseases are considered, including: Pathogenesis Clinical features Pharmacology and treatment Diagnosis Epidemiology Vector biology Vaccinology and prevention Demographic, ecological and social determinants Public health and policy aspects (including cost-effectiveness analyses).