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Host Immune Responses in the Control of Leishmania Infection and...
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Host Immune Responses in the Control of Leishmania Infection and New Forms of Therapy for Tegumentary Leishmaniasis

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Parasitic Pathogens".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 3371

Special Issue Editors

Prof. Dr. Edgar Carvalho

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Guest Editor
Serviço de Imunologia, Complexo Hospitalar Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil
Interests: the immunopathogenisis of leishmaniasis; influence of helminthiasis in immune response of chronic inflammatory diseases and autoimmune diseases; immunotherapy in infectious diseases
Prof. Dr. Walderez Ornelas Dutra

E-Mail Website
Guest Editor
Head of the Cell–Cell Interactions Laboratory, Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Brazil
Interests: immunoregulation of neglected tropical diseases, in particular Chagas disease, leishmaniasis and rheumatic heart disease; biomarkers of disease progression and severity and new immunotherapeutic approaches
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Immunologic responses in the different clinical forms of leishmaniasis vary considerably depending the species of leishmania, genotypic differences intraspecies, and clinical forms of the diseases (including visceral, cutaneous, mucosal, disseminated leishmaniasis, and diffuse cutaneous leishmaniasis). Moreover, about 20% of healthy subjects who reside in endemic areas have evidence of leishmania infection, but do not develop any disease. These individuals are considered to have asymptomatic or subclinical (SC) infection. There is a gap in the understanding of how some subjects control leishmanial infection, while in others the parasites proliferate and consequently develop disease. Additionally, it is not clear why parasites are easily detectable infections caused by some leishmania species such as Leishmania Viannia guyanensis and are scarce in diseases caused by L. braziliensis, as well as why parasites persist in macrophages despite the presence of the Th1 immune response. In American tegumentary leishmaniasis caused by L. braziliensis infection, macrophages produce reactive oxygen species and nitric oxide but have a limited ability to kill leishmania. In contrast, macrophages from subjects with SC infection are less permissive to leishmania penetration and kill parasites, even in the absence of a Th1 immune response. In subjects cured of CL, the ability to control leishmanial infection is restored and, despite the observation of a poor immune response in peripheral blood, there is a strong DTH to leishmania antigens. In mice, resident memory T cells, together with macrophages, control a new infection, but this subject has not been studied in humans.

Treatment failure in tegumentary leishmaniasis is on the rise and chemotherapy associated with immunostimulants or drugs that down-modulate inflammatory responses can enhance the cure rate and decrease the healing time of ulcers.   

The focus of this Special Issue is to show how the immune response controls or facilitates parasite multiplication in human cells and the use of immunotherapy and chemotherapy in the treatment of tegumentary leishmaniasis.

Prof. Dr. Edgar Carvalho
Prof. Dr. Walderez Ornelas Dutra
Guest Editors

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Keywords

  • leishmania killing
  • macrophages
  • dermal memory T cells
  • subclinical leishmania infection
  • cutaneous leishmaniasis

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Published Papers (3 papers)

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Research

21 pages, 10027 KiB  
Article
Intraperitoneal Administration of 17-DMAG as an Effective Treatment against Leishmania braziliensis Infection in BALB/c Mice: A Preclinical Study
by Kercia P. Cruz, Antonio L. O. A. Petersen, Marina F. Amorim, Alan G. S. F. Pinho, Luana C. Palma, Diana A. S. Dantas, Mariana R. G. Silveira, Carine S. A. Silva, Ana Luiza J. Cordeiro, Izabella G. Oliveira, Gabriella B. Pita, Bianca C. A. Souza, Gilberto C. Bomfim, Cláudia I. Brodskyn, Deborah B. M. Fraga, Isadora S. Lima, Maria B. R. de_Santana, Helena M. P. Teixeira, Juliana P. B. de_Menezes, Washington L. C. Santos and Patrícia S. T. Verasadd Show full author list remove Hide full author list
Pathogens 2024, 13(8), 630; https://doi.org/10.3390/pathogens13080630 - 27 Jul 2024
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Abstract
Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in [...] Read more.
Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. Objective: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutaneous leishmaniasis through in vitro and in vivo approaches. Materials and Methods: We assessed 17-DMAG’s cytotoxic effect on bone marrow-derived macrophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound’s efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction in lesion size and the decrease in parasite load in the ears and lymph nodes of infected animals. Results: 17-DMAG showed selective toxicity [selective index = 432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and resulted in parasite clearance from ears and lymph nodes. It also diminished inflammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-γ, TNF) and the regulatory cytokine IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. Conclusions: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases. Full article
(This article belongs to the Special Issue Host Immune Responses in the Control of Leishmania Infection and New Forms of Therapy for Tegumentary Leishmaniasis)
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14 pages, 2203 KiB  
Article
The Role of Senescent CD8+T Cells in the Pathogenesis of Disseminated Leishmaniasis
by Cayo A. Abreu, Maurício Teixeira Nascimento, Olívia Bacellar, Lucas Pedreira Carvalho, Edgar Marcelino Carvalho and Thiago Marconi Cardoso
Pathogens 2024, 13(6), 460; https://doi.org/10.3390/pathogens13060460 - 29 May 2024
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Abstract
Disseminated leishmaniasis (DL) caused by L. braziliensis is characterized by the presence of 10 to more than 1000 lesions spread on the body. While protection against Leishmania is mediated by macrophages upon activation by IFN-γ produced by CD4+T cells, the pathology [...] Read more.
Disseminated leishmaniasis (DL) caused by L. braziliensis is characterized by the presence of 10 to more than 1000 lesions spread on the body. While protection against Leishmania is mediated by macrophages upon activation by IFN-γ produced by CD4+T cells, the pathology of disseminated leishmaniasis (DL) could be mediated by macrophages, NK, and CD8+T cells. Herein, we evaluate the participation of senescent CD8+T cells in the pathogenesis of DL. Methods: Peripheral blood mononuclear cells (PBMCs), biopsies, co-cultures of CD8+T cells with uninfected and infected macrophages (MØ), and PBMC cultures stimulated with soluble L. braziliensis antigen (SLA) for 72 h from patients with cutaneous leishmaniasis (CL) and DL were used to characterize senescent CD8+T cells. Statistical analysis was performed using the Mann–Whitney and Kruskal–Wallis tests, followed by Dunn’s. Results: Patients with DL have an increase in the frequency of circulating CD8+T cells that present a memory/senescent phenotype, while lesions from DL patients have an increase in the frequency of infiltrating CD8+T cells with a senescent/degranulation phenotype. In addition, after specific stimuli, DL patients’ circulating CD8+T with memory/senescent profile, showing degranulation characteristics, increased upon SLA stimuli, and those specific CD8+T cells from DL patients had an increased degranulation phenotype, causing more apoptosis of infected target cells. Conclusions: DL patients show a higher frequency of cytotoxic senescent CD8+T cells compared to CL patients, and that could promote the lysis of infected cells, although without parasite killing, releasing Leishmania to the extracellular compartment, contributing to the spread of parasites. Full article
(This article belongs to the Special Issue Host Immune Responses in the Control of Leishmania Infection and New Forms of Therapy for Tegumentary Leishmaniasis)
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10 pages, 990 KiB  
Article
Improved Treatment Outcome Following the Use of a Wound Dressings in Cutaneous Leishmaniasis Lesions
by Pedro B. Borba, Jamile Lago, Tainã Lago, Mariana Araújo-Pereira, Artur T. L. Queiroz, Hernane S. Barud, Lucas P. Carvalho, Paulo R. L. Machado, Edgar M. Carvalho and Camila I. de Oliveira
Pathogens 2024, 13(5), 416; https://doi.org/10.3390/pathogens13050416 - 16 May 2024
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Abstract
Leishmaniasis, caused by Leishmania parasites, is a neglected tropical disease and Cutaneous Leishmaniasis (CL) is the most common form. Despite the associated toxicity and adverse effects, Meglumine antimoniate (MA) remains the first-choice treatment for CL in Brazil, pressing the need for the development [...] Read more.
Leishmaniasis, caused by Leishmania parasites, is a neglected tropical disease and Cutaneous Leishmaniasis (CL) is the most common form. Despite the associated toxicity and adverse effects, Meglumine antimoniate (MA) remains the first-choice treatment for CL in Brazil, pressing the need for the development of better alternatives. Bacterial NanoCellulose (BNC), a biocompatible nanomaterial, has unique properties regarding wound healing. In a previous study, we showed that use of topical BNC + systemic MA significantly increased the cure rate of CL patients, compared to treatment with MA alone. Herein, we performed a study comparing the combination of a wound dressing (BNC or placebo) plus systemic MA versus systemic MA alone, in CL caused by Leishmania braziliensis. We show that patients treated with the combination treatment (BNC or placebo) + MA showed improved cure rates and decreased need for rescue treatment, although differences compared to controls (systemic MA alone) were not significant. However, the overall time-to-cure was significantly lower in groups treated with the combination treatment (BNC+ systemic MA or placebo + systemic MA) in comparison to controls (MA alone), indicating that the use of a wound dressing improves CL treatment outcome. Assessment of the immune response in peripheral blood showed an overall downmodulation in the inflammatory landscape and a significant decrease in the production of IL-1a (p < 0.05) in patients treated with topical BNC + systemic MA. Our results show that the application of wound dressings to CL lesions can improve chemotherapy outcome in CL caused by L. braziliensis. Full article
(This article belongs to the Special Issue Host Immune Responses in the Control of Leishmania Infection and New Forms of Therapy for Tegumentary Leishmaniasis)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: The role of senescent CD8+ T cells in the pathogenesis of dis-seminated leishmaniasis
Author: CARDOSO
Highlights: Disseminated Leishmaniasis; CD8+T cells; senescent.

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