Arginase/nitric oxide modifications using live non-pathogenic Leishmania tarentolae as an effective delivery system inside the mammalian macrophages

Badirzadeh, Alireza; Montakhab-Yeganeh, Hossein; Miandoabi, Touraj

doi:10.1007/s12639-020-01279-5

Cited by 7 publications

(6 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, most of the subsequent studies suggested the need to co-administer appropriate adjuvants, or to engineer Leishmania for the expression of immune-modulating molecules to activate a polarized Th1 response (e.g., [ 16 , 21 ]). Conversely, evidence for the expression of M2 markers in human macrophages, after stimulation with L. tarentolae , has also been reported [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Leishmania tarentolae as an Antigen Delivery Platform: Dendritic Cell Maturation after Infection with a Clone Engineered to Express the SARS-CoV-2 Spike Protein

et al. 2022

View full text Add to dashboard Cite

Background: Protozoa of the genus Leishmania are characterized by their capacity to target macrophages and Dendritic Cells (DCs). These microorganisms could thus be exploited for the delivery of antigens to immune cells. Leishmania tarentolae is regarded as a non-pathogenic species; it was previously used as a biofactory for protein production and has been considered as a candidate vaccine or as an antigen delivery platform. However, results on the type of immune polarization determined by L. tarentolae are still inconclusive. Methods: DCs were derived from human monocytes and exposed to live L. tarentolae, using both the non-engineered P10 strain, and the same strain engineered for expression of the spike protein from SARS-CoV-2. We then determined: (i) parasite internalization in the DCs; and (ii) the capacity of the assayed strains to activate DCs and the type of immune polarization. Results: Protozoan parasites from both strains were effectively engulfed by DCs, which displayed a full pattern of maturation, in terms of MHC class II and costimulatory molecule expression. In addition, after parasite infection, a limited release of Th1 cytokines was observed. Conclusions: Our results indicate that L. tarentolae could be used as a vehicle for antigen delivery to DCs and to induce the maturation of these cells. The limited cytokine release suggests L. tarentolae as a neutral vaccine vehicle that could be administered in association with appropriate immune-modulating molecules.

show abstract

Section: Introductionmentioning

confidence: 99%

Leishmania tarentolae as an Antigen Delivery Platform: Dendritic Cell Maturation after Infection with a Clone Engineered to Express the SARS-CoV-2 Spike Protein

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The increase in the antileishmanial activity observed for compound 4 , comparing promastigote and intracellular amastigote assays results, might be a suggestion of an indirect mechanism of action on infected cells, in addition to the direct action on promastigote forms also detected by transmission electron microscopy. There are several forms of a molecule that indirectly act against intracellular parasites, NO induction being one of the most effective, , especially against Leishmania. , NO acts on pathogenic microorganisms by the inhibition of proliferation, induction of DNA mutagenesis, disruption of [FeS] clusters, metabolic blockade, and inactivation of virulence factors. , Therefore, we evaluated the role of NO induction in macrophages treated with compound 4 .…”

Section: Discussionmentioning

confidence: 99%

“…There are several forms of a molecule that indirectly act against intracellular parasites, NO induction being one of the most effective, 39,40 especially against Leishmania. 41,42 NO acts on pathogenic microorganisms by the inhibition of proliferation, induction of DNA mutagenesis, disruption of [FeS] clusters, metabolic blockade, and inactivation of virulence factors. 21,43 Therefore, we evaluated the role of NO induction in macrophages treated with compound 4.…”

Section: ■ Discussionmentioning

confidence: 99%

Nitric Oxide Induction in Peritoneal Macrophages by a 1,2,3-Triazole Derivative Improves Its Efficacy upon Leishmania amazonensis In Vitro Infection

et al. 2021

View full text Add to dashboard Cite

1,2,3-Triazole is one of the most flexible chemical scaffolds broadly used in various fields. Here, we report the antileishmanial activity of 1,2,3-triazole derivatives, the ultrastructural alterations induced by their treatment, and the nitric oxide (NO) modulation effect on their efficacy against Leishmania amazonensis in vitro infection. After the screening of eleven compounds, compound 4 exhibited better results against L. amazonensis promastigotes (IC50 = 15.52 ± 3.782 μM) and intracellular amastigotes (IC50 = 4.10 ± 1.136 μM), 50% cytotoxicity concentration at 84.01 ± 3.064 μM against BALB/c peritoneal macrophages, and 20.49-fold selectivity for the parasite over the cells. Compound 4 induced ultrastructural mitochondrial alterations and lipid inclusions in L. amazonensis promastigotes, upregulated tumor necrosis factor α, interleukin (IL)-1β, IL-6, IL-12, and IL-10 messenger RNA expressions, and enhanced the NO production, verified by nitrite (p = 0.0095) and inducible nitric oxide synthase expression (p = 0.0049) quantification, which played an important role in its activity against intramacrophagic L. amazonensis. In silico prediction in association with antileishmanial activity results showed compound 4 as a hit compound with promising potential for further studies of new leishmaniasis treatment options.

show abstract

“…Arginase activity were carried out in the FPs of those mice used for splenocyte culture preparation. The arginase activity test quantifies the conversion of L-arginine to L-ornithine, as described elsewhere [ 2 , 30 ]. NO production measurement was carried out by applying the protocol of the Griess Reagent System (Promega, Madison, WI).…”

Section: Methodsmentioning

confidence: 99%

“…After a10 min incubation at room temperature, the colored (azo dye) complex absorbance was measured at an OD = 570 nm. The NO absorbance values of each sample were quantified in terms of standard curve of nitrate [ 2 , 30 , 31 ].…”

Section: Methodsmentioning

confidence: 99%

Effects of negative air ions (NAIs) on Leishmania major: A novel tool for treatment of zoonotic cutaneous leishmaniasis (ZCL)

et al. 2022

Self Cite

View full text Add to dashboard Cite

Background Cutaneous leishmaniasis (CL) is a Neglected Tropical Disease (NTD) that causes high morbidity in the tropics and sub-tropics. Despite the remarkable advancements in the treatment of CL, the available therapeutics are far from ideal and also cause serious adverse side effects. Negative air ions (NAIs) generators are widely available for domestic and industrial uses. Several studies have reported on positive effects of NAIs therapy on human health as a non-pharmaceutical treatment for respiratory disease, allergy, or stress-related health conditions, including infectious diseases. To our knowledge, no studies have examined the effectiveness of the NAIs therapy against Leishmania parasites. The aims of this study were to investigate the effect of NAIs therapy on Leishmania major (L. major) the causative agent of CL in in vitro and in a murine model. Methodology/Principal findings In vitro anti-leishmanial effects of NAIs therapy were measured by parasitological methods. NAIs therapy was assessed in vivo in L. major infected BALB/c mice by measuring the footpad (FP) lesion size and parasite load using metric caliper tool and qPCR, respectively. Immune responses in treated and non-treated mice were assessed by measuring the levels of IFN-γ, IL-4, NO and arginase activity. In vitro NAIs therapy significantly decreased the viability of Leishmania promastigotes and of amastigotes cultured in macrophages, but did not affect the host cells. NAIs therapy of L. major infected BALB/c mice resulted in reduced FP lesion size, diminished parasite burden, and importantly decreased induction of IL-4 and arginase activity in the presence of NAIs. In contrast IFN-γ and NO levels were significantly enhanced. NAIs therapy significantly diminished the progression of disease compared to the control group, but was less effective than amphotericin B treatment. Conclusions Our study shows that NAIs treatment was effective in vitro and in Leishmania-infected mice, elicited a T-helper 1 (Th1) response and increased efficient cellular immunity, resulting in a diminished parasite load. Therefore, NAIs therapy can be considered as a useful and safe tool that can contribute to clearing L. major infections without inducing toxicity in host cells. The applications and mechanisms of NAIs therapy warrant further investigation especially in humans suffering from CL.

show abstract

Arginase/nitric oxide modifications using live non-pathogenic Leishmania tarentolae as an effective delivery system inside the mammalian macrophages

Cited by 7 publications

References 41 publications

Leishmania tarentolae as an Antigen Delivery Platform: Dendritic Cell Maturation after Infection with a Clone Engineered to Express the SARS-CoV-2 Spike Protein

Leishmania tarentolae as an Antigen Delivery Platform: Dendritic Cell Maturation after Infection with a Clone Engineered to Express the SARS-CoV-2 Spike Protein

Nitric Oxide Induction in Peritoneal Macrophages by a 1,2,3-Triazole Derivative Improves Its Efficacy upon Leishmania amazonensis In Vitro Infection

Effects of negative air ions (NAIs) on Leishmania major: A novel tool for treatment of zoonotic cutaneous leishmaniasis (ZCL)

Contact Info

Product

Resources

About