scholarly journals Intranasal Vaccination against Cutaneous Leishmaniasis with a Particulated Leishmanial Antigen or DNA Encoding LACK

2004 ◽  
Vol 72 (8) ◽  
pp. 4521-4527 ◽  
Author(s):  
Eduardo Fonseca Pinto ◽  
Roberta Olmo Pinheiro ◽  
Alice Rayol ◽  
Vicente Larraga ◽  
Bartira Rossi-Bergmann
Keyword(s):  
Lymph Nodes ◽  
Cutaneous Leishmaniasis ◽  
Oral Delivery ◽  
Parasite Burden ◽  
Mucosal Vaccine ◽  
Effective Control ◽  
Dna Encoding ◽  
Intranasal Route ◽  
Ifn Γ ◽  
Draining Lymph Nodes

ABSTRACT We have previously demonstrated that oral delivery of a disease-promoting particulated antigen of Leishmania amazonensis (LaAg) partially protects mice against cutaneous leishmaniasis. In the present work, we sought to optimize a mucosal vaccine by using the intranasal route for delivery of different antigen preparations, including (i) LaAg, (ii) soluble recombinant p36/LACK leishmanial antigen (LACK), and (iii) plasmid DNA encoding LACK (LACK DNA). BALB/c mice that received two intranasal doses of 10 μg of LaAg and were challenged 1 week postvaccination with L. amazonensis developed delayed but effective control of lesion growth. A diminished parasite burden was accompanied by enhancement of both gamma interferon (IFN-γ) and interleukin-10 levels in the lesion-draining lymph nodes. The vaccine efficacy improved with time. At 4 months postvaccination, when a strong parasite-specific TH1-type response was present in vivo, the infection was controlled for at least 5 months after challenge. In contrast to the particulated LaAg, soluble LACK (10 μg/dose) had no effect. Interestingly, LACK DNA (30 μg/dose), but not empty DNA, promoted rapid and durable protective immunity. Parasite growth was effectively controlled, and at 5 months after challenge LACK-reactive cells in both the mucosal and lesion-draining lymph nodes produced high levels of IFN-γ. These results demonstrate for the first time the feasibility of using the intranasal route for long-lived memory vaccination against cutaneous leishmaniasis with adjuvant-free crude antigens or DNA.

scholarly journals Investigating the Existence of Ribosomal Protein L5 Gene in Syrian Strain of Leishmania tropica Genome: Sequencing It and Evaluating Its Immune Response as DNA Vaccine

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mohammad Maarouf ◽  
Alyaa A. Abdlwahab
Keyword(s):  
Lymph Nodes ◽  
Ribosomal Protein ◽  
Dna Vaccine ◽  
Parasite Burden ◽  
Leishmania Tropica ◽  
Ifn Γ ◽  
Ribosomal Protein L5 ◽  
Protective Strategies ◽  
Efficacious Vaccine ◽  
Draining Lymph Nodes

Cutaneous leishmaniasis in Syria is caused mainly by Leishmania tropica. It represents a serious health problem, which has aggravated further after the civil war in the country. Until now, there are no effective protective strategies, safe therapy, or efficacious vaccine to protect from this infection. DNA vaccines represent a promising approach for achieving protection against leishmaniasis. The L5 ribosomal protein plays fundamental roles in the assembly process of the ribosome subunits, so this study has chosen the ribosomal protein L5 gene to design a DNA vaccine against Leishmania tropica infection. After proving the existence of the ribosomal protein L5 gene in a Syrian strain of Leishmania tropica (LCED Syrian 01), it was sequenced and cloned into a pCI plasmid, and the designed DNA vaccine was administered to BALB/c mice. The protective response was evaluated by measuring lesion development in immunized BALB/c mice for 6 weeks after challenging mice with the parasite. RT-qPCR was used to quantify IL-12, IFN-γ, and IL-4 in draining lymph nodes (DLNs) of immunized mice. In the final week, the parasite burden was determined in footpad lesions and local draining lymph nodes (DLNs). This study demonstrated the presence and expression of the ribosomal protein L5 gene in the Syrian strain of Leishmania tropica promastigotes. The sequence of the ribosomal protein cDNA L5 gene was determined and published in Genbank. The gene size was 918 bp. Expression was also demonstrated at the level of cDNA. This study also demonstrated that vaccination with the ribosomal protein L5 gene induces TH1 response in immunized mice. This response prevents the partial development of a skin lesion of Leishmania.

scholarly journals Subcutaneous immunization against Leishmania major - infection in mice: efficacy of formalin-killed promastigotes combined with adjuvants

2010 ◽  
Vol 52 (2) ◽  
pp. 95-100 ◽  
Author(s):  
Joshua M. Mutiso ◽  
John C. Macharia ◽  
Rosemary M. Mutisya ◽  
Evans Taracha
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Immune Status ◽  
Parasite Burden ◽  
Interferon Γ ◽  
Cutaneous Lesions ◽  
Ifn Γ ◽  
Efficacious Vaccine ◽  
Subcutaneous Immunization ◽  
Murine Cutaneous Leishmaniasis

Formalin-killed promastigotes (FKP) of Leishmania major, in combination with Montanide ISA 720 (MISA), BCG or alum were used in vaccination of an inbred murine model against cutaneous leishmaniasis (CL). Significant and specific increases in anti-FKP IgG responses were detected for both alum-FKP and BCG-FKP compared to MISA-FKP (p < 0.001). Significant increases in splenic lymphocyte recall proliferation was obtained in the MISA-FKP vaccinated mice compared to alum-FKP or BCG-FKP vaccinated groups (p < 0.01). The highest interferon-γ responses were observed in the BCG-FKP group followed by the MISA-FKP while the alum-FKP gave the least responses. Significantly reduced lesion sizes were obtained in the MISA-FKP group compared to the BCG/alum adjuvants-FKP vaccinated groups. Although the BCG-FKP group showed the highest IFN-γ responses, it failed to control cutaneous lesions. Significant reductions in parasite numbers were observed in the MISA-FKP and BCG-FKP vaccinated groups (p < 0.001). There was a good correlation between parasite burden and IFN-γ level indicating IFN-γ response as a sensitive parameter of the immune status. In conclusion, MISA-FKP is the most efficacious vaccine formulation against murine cutaneous leishmaniasis.

Lymphocyte Phenotypes and HLA-DR Expression in the Lesions of Cutaneous Leishmaniasis and Their Draining Lymph Nodes

1987 ◽  
Vol 7 (3) ◽  
pp. 212-220 ◽  
Author(s):  
Ahmed M. El-Hassan ◽  
Raj Kubba ◽  
Yusuf M. Al-Gindan ◽  
Abdelhamid S. Omer ◽  
Methil K. Kutty ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Cutaneous Leishmaniasis ◽  
Hla Dr ◽  
Lymphocyte Phenotypes ◽  
Draining Lymph Nodes

Determination of a CD4+CD25−FoxP3+ T cells subset in tumor-draining lymph nodes of colorectal cancer secreting IL-2 and IFN-γ

Tumor Biology ◽  
2016 ◽  
Vol 37 (11) ◽  
pp. 14659-14666 ◽  
Author(s):  
Morteza Jafarinia ◽  
Fereshteh Mehdipour ◽  
Seyed Vahid Hosseini ◽  
Leila Ghahramani ◽  
Masood Hosseinzadeh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Lymph Nodes ◽  
Ifn Γ ◽  
Draining Lymph Nodes

scholarly journals Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection

2017 ◽  
Vol 85 (3) ◽  
Author(s):  
Allison K. Ehrlich ◽  
Olga L. Fernández ◽  
Daniel Rodriguez-Pinto ◽  
Tiago M. Castilho ◽  
Maria J. Corral Caridad ◽  
...  
Keyword(s):  
B Cells ◽  
Mouse Model ◽  
Cutaneous Leishmaniasis ◽  
Transforming Growth Factor ◽  
Parasite Burden ◽  
Cell Populations ◽  
High Dose ◽  
Toll Like Receptor ◽  
Content Type ◽  
Ifn Γ

ABSTRACT Infection by Leishmania (Viannia) panamensis, the predominant etiologic agent for cutaneous leishmaniasis in Colombia, is characterized by a chronic mixed inflammatory response. Current treatment options are plagued by toxicity, lengthy treatment regimens, and growing evidence of drug resistance. Immunotherapy, modulating the immune system to mount a protective response, may provide an alternate therapeutic approach. We investigated the ability of the Toll-like receptor 9 (TLR9) ligand CpG to modulate established disease in the L. (V.) panamensis mouse model. Treatment of established infection with a high dose (50 μg) of CpG ameliorated disease and lowered parasite burden. Interestingly, immediately after treatment there was a significant increase in transforming growth factor β (TGF-β) and concomitantly an increase in T regulatory cell (Treg) function. Although a general reduction in cell-mediated immune cytokine and chemokine (gamma interferon [IFN-γ], interleukin 10 [IL-10], IL-13, IL-6, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-4, and MIP-1α) responses of the treated mice was observed, certain chemokines (RANTES, monocyte chemoattractant protein 1[MCP-1], and IP-10) were increased. Further, in peripheral blood mononuclear cells (PBMCs) from patients with cutaneous leishmaniasis, CpG treatment similarly exhibited a dose-response effect on the production of IFN-γ, IL-17, IL-10, and IL-13, with reductions observed at higher doses. To further understand the underlying mechanisms and cell populations driving the CpG mediated response, we examined the ex vivo dose effects mediated by the TLR9+ cell populations (dendritic cells, macrophages, and B cells) found to accumulate labeled CpG in vivo. Notably, B cells altered the production of IL-17, IL-13, and IFN-γ, supporting a role for B cells functioning as antigen-presenting cells (APCs) and/or regulatory cells during infection. Interestingly, B cells have been previously demonstrated as a primary type of APC in patients infected with L. (V.) panamensis and thus may be useful targets of immunotherapy. Collectively, our results show that CpG-induced immune regulation leads to a dampening of the host immune response and healing in the mouse model, and it may provide an alternate approach to treatment of cutaneous leishmaniasis caused by L. (V.) panamensis.

Activity of antimalarial drugs in vitro and in a murine model of cutaneous leishmaniasis

2013 ◽  
Vol 62 (7) ◽  
pp. 1001-1010 ◽  
Author(s):  
Vinícius Pinto Costa Rocha ◽  
Fabiana Regina Nonato ◽  
Elisalva Teixeira Guimarães ◽  
Luiz Antônio Rodrigues de Freitas ◽  
Milena Botelho Pereira Soares
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Parasite Burden ◽  
Lesion Size ◽  
Oral Route ◽  
Antimalarial Drugs ◽  
Endocytic Pathway ◽  
Multivesicular Bodies ◽  
Draining Lymph Nodes

The currently used treatments for leishmaniasis, a neglected parasitic disease, are associated with several side effects, high cost and resistance of the Leishmania parasites. Here we evaluated in vitro and in vivo the antileishmanial activity of five antimalarial drugs against Leishmania amazonensis. Mefloquine was effective against promastigotes in axenic cultures and showed an IC50 (concentration giving half-maximal inhibition) value of 8.4±0.7 µM. In addition, mefloquine, chloroquine and hydroxychloroquine were active against intracellular amastigotes in macrophage-infected cultures, presenting IC50 values of 1.56±0.19 µM, 0.78±0.08 µM and 0.67±0.12 µM, respectively. The ultrastructural analysis of chloroquine- or mefloquine-treated amastigotes showed an accumulation of multivesicular bodies in the cytoplasm of the parasite, suggesting endocytic pathway impairment, in addition to the formation of myelin-like figures and enlargement of the Golgi cisternae. CBA mice were infected with L. amazonensis in the ear dermis, and treated by oral and/or topical routes with chloroquine and mefloquine. Treatment of L. amazonensis-infected mice with chloroquine by the oral route reduced lesion size, which was associated with a decrease in the number of parasites in the ear, as well as the parasite burden in the draining lymph nodes. In contrast, mefloquine administration by both routes decreased the lesion size in infected mice without causing a reduction in parasite burden. Our results revealed a promising antileishmanial effect of chloroquine and suggest its use in cutaneous leishmaniasis treatment.

scholarly journals Enrichment of Innate Lymphoid Cell Populations in Gingival Tissue

2018 ◽  
Vol 97 (12) ◽  
pp. 1399-1405 ◽  
Author(s):  
J.L. Brown ◽  
L. Campbell ◽  
J. Malcolm ◽  
A. Adrados Planell ◽  
J.P. Butcher ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Lymph Nodes ◽  
Population Group ◽  
Lymphoid Cells ◽  
Gingival Tissue ◽  
Regional Lymph Nodes ◽  
Mucosal Surfaces ◽  
Ifn Γ ◽  
Draining Lymph Nodes ◽  
Group 1

Innate lymphoid cells (ILCs) are a population of lymphocytes that act as the first line of immunologic defense at mucosal surfaces. The ILC family in the skin, lungs, and gastrointestinal tissues has been investigated, and there are reports of individual subsets of ILCs in the oral tissues. We sought to investigate the whole ILC population (group 1, 2, and 3 subsets) in the murine gingivae and the lymph nodes draining the oral cavity. We show that ILCs made up a greater proportion of the whole CD45+ lymphocyte population in the murine gingivae (0.356% ± 0.039%) as compared with the proportion of ILCs in the draining lymph nodes (0.158% ± 0.005%). Cytokine profiling of the ILC populations demonstrated different proportions of ILC subsets in the murine gingivae versus the regional lymph nodes. The majority of ILCs in the draining lymph nodes expressed IL-5, whereas there were equal proportions of IFN-γ- and IL-5 expressing ILCs in the oral mucosa. The percentage of IL-17+ ILCs was comparable between the murine gingivae and the oral draining lymph nodes. These data suggest an enrichment of ILCs in the murine gingivae, and these ILCs reflect a cytokine profile discrepant to that of the local draining lymph nodes. These studies indicate diversity and enrichment of ILCs at the oral mucosal surface. The function of ILCs in the oral cavity remains to be determined; here, we provide a premise of ILC populations that merits future consideration in investigations of mouse models and human tissues.

scholarly journals Gene Transcription Profile in Mice Vaccinated with Ultraviolet-attenuated Cercariae of Schistosoma japonicum Reveals Molecules Contributing to Elevated IFN-γ Levels

2005 ◽  
Vol 37 (4) ◽  
pp. 254-264 ◽  
Author(s):  
Xiang Zhu ◽  
Zhao-Song Zhang ◽  
Min-Jun Ji ◽  
Hai-Wei Wu ◽  
Yong Wang ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Schistosoma Japonicum ◽  
Protective Immunity ◽  
Early Stage ◽  
Post Vaccination ◽  
Ifn Γ ◽  
Preliminary Study ◽  
Gene Transcription Profile ◽  
Th1 And Th2 Responses ◽  
Draining Lymph Nodes

AbstractVaccination with ultraviolet-attenuated cercariae of Schistosoma japonicum induced protective immunity against challenge infection in experimental animal models. Our preliminary study on the transcription levels of IFN-γ and IL-4 in splenic CD4+ T cells revealed that attenuated cercariae elicited predominantly a Th1 response in mice at the early stage, whereas normal cercariae stimulated primarily Independent responses. Further analysis on the gene profile of the skin-draining lymph nodes demonstrated that the levels of IFN-γ were significantly higher in vaccinated mice than those in infected mice at day 4, 7 and 14 post-vaccination or post-infection. However, for IL-12 and IL-4, the potent inducers of Th1 and Th2 responses, respectively, as well as IL-10, there were no differences over the course of the experiment between the infected and vaccinated mice. To explore the underlying factors that may potentially contribute to elevated IFN-γ in vaccinated mice, the mRNA profiles of the skin-draining lymph nodes at day 4 post-exposure were compared using oligonucleotide microarrays. Within the 847 probe sets with increased signal values, we focused on chemokines, cytokines and relevant receptors, which were validated by semi-quantitative RT-PCR. A comprehensive understanding of the immune mechanisms of attenuated cercariae-induced protection may contribute to developing efficient vaccination strategies against S. japonicum, especially during the early stage of infection.

scholarly journals Protection induced by anti-PD-1 and anti-PD-L1 treatment in Leishmania amazonensis-infected BALB/c mice

2019 ◽  
Author(s):  
Alessandra M. da Fonseca-Martins ◽  
Tadeu D. Ramos ◽  
Juliana E.S. Pratti ◽  
Luan Firmino-Cruz ◽  
Daniel Claudio Oliveira Gomes ◽  
...  
Keyword(s):  
T Cells ◽  
Cutaneous Leishmaniasis ◽  
Therapeutic Potential ◽  
Parasite Burden ◽  
Current Treatment ◽  
Leishmania Amazonensis ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Ifn Γ ◽  
Antigen Presenting

AbstractLeishmaniasis is a neglected disease, for which current treatment presents numerous issues. Leishmania amazonensis is the etiological agent of cutaneous and diffuse cutaneous leishmaniasis. The roles of the programmed death-1 (PD-1) receptor on lymphocytes and its ligand (PD-L1) on antigen-presenting cells have been well studied in tumor and other infection models; but little is known about their roles in non-healing cutaneous leishmaniasis. Our previous report of L. amazonensis-induced PD-L1 expression on dendritic cells, in combination with decreased IFN-γ production by CD4+ T cells in C57BL/6 mice, led to a hypothesis that the formation of the PD-1/PD-L1 complex contributes to down-modulation of immune responses, especially T cell suppression, enabling parasite survival and persistence. In this study, we tested the therapeutic potential of anti-PD-1 and anti-PD-L1 monoclonal antibodies (MoAbs) against a non-healing L. amazonensis infection in BALB/c mice. We observed that L. amazonensis induced PD-1 expression on both CD4+ and CD8+ T cells, and that anti-PD-1 and anti-PD-L1 treatment significantly increased IFN-γ-producing CD4+ and CD8+ T cells, respectively. Compared with infection controls, mice that received treatment with anti-PD-1 and anti-PD-L1, but not anti-PD-L2, displayed bigger lesions with significantly lower parasite loads. Treatment did not affect anti-Leishmania antibody or IL-10 production, but anti-PD-1 treatment reduced both IL-4 and TGF-β production. Together, our results highlight the therapeutic potential of an anti-PD-1-based treatment in promoting the reinvigoration of T cells for the control of parasite burden.

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