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TropicalMed
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Advances in Cell Biology and Immunology of Leishmania
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Advances in Cell Biology and Immunology of Leishmania

A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366). This special issue belongs to the section "Vector-Borne Diseases".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 17836

Special Issue Editor

Dr. Tatjana Souza Lima Keesen

E-Mail Website
Guest Editor
Department of Cellular and Molecular Biology, Federal University of Paraiba, João Pessoa 58051-900, Brazil
Interests: immune responses; pathogenesis diagnosis and treatment of Leishmaniasis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Leishmaniasis is a group of infectious and parasitic diseases caused by trypanosomatid protozoa of the genus Leishmania, which is within the group of neglected tropical diseases. Immunological responses are diverse depending on Leishmania species. Clues about immune biomarkers in a set of these diseases are important to clear immune therapy studies in neglected diseases such as leishmaniases. Despite the traditional view of immune T cell response as a hallmark of the adaptive immune system, much attention has been given to the phenomenon of long-term adaptation of the innate system, namely trained immunity. Characterizing adaptative and innate immune markers, the pattern of expression, and their possibility to aid the improvement of investments in the investigation of new treatments with fewer side effects and greater patient compliance is of great importance in this area. Therefore, studies that could cover immunological aspects and improvements for treatments in this area would be important. This Special Issue aims to serve as a comprehensive collection of studies on the participation of immune responses in the immunopathogenesis of leishmaniasis. Both human and animal model studies are welcome in this issue. In this collection, we welcome review articles, original research, and critical reviews addressing the contributions of the Leishmania field. Articles focused on the following aspects are highly encouraged:

  • Development of T and B lymphocytes in the immunopathogenesis of leishmaniasis;
  • Innate immune responses in leishmaniasis;
  • Molecular and cellular aspects of leishmaniasis;
  • Epigenetic and metabolic reprogramming of immune cells in leishmaniasis;
  • Immune cells as therapeutic targets and biomarkers for prediction/diagnosis of leishmaniasis.

Dr. Tatjana Souza Lima Keesen
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Leishmania sp.
  • innate immune response
  • adaptative immune response
  • therapeutic
  • diagnosis

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Published Papers (6 papers)

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Research

Jump to: Review, Other

17 pages, 2429 KiB  
Article
Gene Expression Profiling of Classically Activated Macrophages in Leishmania infantum Infection: Response to Metabolic Pre-Stimulus with Itaconic Acid
by Génesis Palacios, Elva Vega-García, Basilio Valladares, José Antonio Pérez, Roberto Dorta-Guerra and Emma Carmelo
Trop. Med. Infect. Dis. 2023, 8(5), 264; https://doi.org/10.3390/tropicalmed8050264 - 3 May 2023
Cited by 1 | Viewed by 2193
Abstract
Leishmania infection of phagocytic cells, such as macrophages, induces the differentiation of infected cells into different phenotypes according to their surrounding microenvironments. The classical activation of macrophages involves metabolic reprogramming, in which several metabolites such as succinate, fumarate and itaconate are accumulated. The [...] Read more.
Leishmania infection of phagocytic cells, such as macrophages, induces the differentiation of infected cells into different phenotypes according to their surrounding microenvironments. The classical activation of macrophages involves metabolic reprogramming, in which several metabolites such as succinate, fumarate and itaconate are accumulated. The immunoregulatory functions of itaconate in the context of Leishmania infection were investigated in this paper. Ex vivo bone marrow-derived macrophages were differentiated into classically activated macrophages through IFNG activation and infection with Leishmania infantum. A high-throughput real-time qPCR experiment was designed for the analyses of 223 genes involved in immune response and metabolism. The transcriptional profile of classically activated macrophages revealed the enrichment of the IFNG response pathways and the upregulation of genes such as Cxcl9, Irf1, Acod1, Il12b, Il12rb1, Nos2 or Stat1. In vitro pre-stimulation with itaconate induced a loss of the parasite control and the upregulation of genes related to local acute inflammatory response. Our results reveal that itaconate accumulation dampened classically activated macrophage antiparasitic activity, and this is reflected by the differential expression of the Il12b, Icosl and Mki67 genes. The possibility of inducing parasite-killing responses in the host through metabolic reprograming is an interesting approach for the treatment of Leishmania infections that will undoubtedly attract increasing attention in the coming years. Full article
(This article belongs to the Special Issue Advances in Cell Biology and Immunology of Leishmania)
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15 pages, 3672 KiB  
Article
Leishmanicidal Activity of Guanidine Derivatives against Leishmania infantum
by Fernanda Silva Almeida, Vitor Partite Moreira, Edson dos Santos Silva, Leonardo Lima Cardoso, Pedro Henrique de Sousa Palmeira, Luiz Henrique Agra Cavalcante-Silva, Demétrius A. M. de Araújo, Ian P. G. do Amaral, Eduardo René Pérez González and Tatjana S. L. Keesen
Trop. Med. Infect. Dis. 2023, 8(3), 141; https://doi.org/10.3390/tropicalmed8030141 - 25 Feb 2023
Cited by 7 | Viewed by 2368
Abstract
Leishmaniasis is a neglected tropical infectious disease with thousands of cases annually; it is of great concern to global health, particularly the most severe form, visceral leishmaniasis. Visceral leishmaniasis treatments are minimal and have severe adverse effects. As guanidine-bearing compounds have shown antimicrobial [...] Read more.
Leishmaniasis is a neglected tropical infectious disease with thousands of cases annually; it is of great concern to global health, particularly the most severe form, visceral leishmaniasis. Visceral leishmaniasis treatments are minimal and have severe adverse effects. As guanidine-bearing compounds have shown antimicrobial activity, we analyzed the cytotoxic effects of several guanidine-bearing compounds on Leishmania infantum in their promastigote and amastigote forms in vitro, their cytotoxicity in human cells, and their impact on reactive nitrogen species production. LQOFG-2, LQOFG-6, and LQOFG-7 had IC50 values of 12.7, 24.4, and 23.6 µM, respectively, in promastigotes. These compounds exhibited cytotoxicity in axenic amastigotes at 26.1, 21.1, and 18.6 µM, respectively. The compounds showed no apparent cytotoxicity in cells from healthy donors. To identify mechanisms of action, we evaluated cell death processes by annexin V and propidium iodide staining and nitrite production. Guanidine-containing compounds caused a significant percentage of death by apoptosis in amastigotes. Independent of L. infantum infection, LQOFG-7 increased nitrite production in peripheral blood mononuclear cells, which suggests a potential mechanism of action for this compound. Therefore, these data suggest that guanidine derivatives are potential anti-microbial molecules, and further research is needed to fully understand their mechanism of action, especially in anti-leishmanial studies. Full article
(This article belongs to the Special Issue Advances in Cell Biology and Immunology of Leishmania)
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12 pages, 1923 KiB  
Article
Characterization of Regulatory T Cells in Patients Infected by Leishmania Infantum
by Rephany F. Peixoto, Bruna M. Gois, Marineuma Martins, Pedro Henrique S. Palmeira, Juliana C. Rocha, Juliana A. S. Gomes, Fátima L. A. A. Azevedo, Robson C. Veras, Isac A. de Medeiros, Teresa C. S. L. Grisi, Demétrius A. M. de Araújo, Ian P. G. Amaral and Tatjana S. L. Keesen
Trop. Med. Infect. Dis. 2023, 8(1), 18; https://doi.org/10.3390/tropicalmed8010018 - 27 Dec 2022
Cited by 2 | Viewed by 2851
Abstract
High IL-10 levels are pivotal to parasite survival in visceral leishmaniasis (VL). Antigenic stimuli induce IL-10 expression and release of adenosine by CD39/CD73. Due their intrinsic ability to express IL-10 and produce adenosine from extracellular ATP, we evaluated the IL-10, CD39, and CD73 [...] Read more.
High IL-10 levels are pivotal to parasite survival in visceral leishmaniasis (VL). Antigenic stimuli induce IL-10 expression and release of adenosine by CD39/CD73. Due their intrinsic ability to express IL-10 and produce adenosine from extracellular ATP, we evaluated the IL-10, CD39, and CD73 expression by Regulatory T cells (Treg) correlated with VL pathology. Using flow cytometry, Treg cells was analyzed in peripheral blood samples from VL patients (in the presence and absence of Leishmania infantum soluble antigen (SLA)) and healthy individuals (negative endemic control—NEC group), without any treatment. Additionally, IL-10 levels in leukocytes culture supernatant were measured in all groups by ELISA assay. VL patients presented more Treg frequency than NEC group, independently of stimulation. ELISA results demonstrated that SLA induced higher IL-10 expression in the VL group. However, the NEC group had a higher Treg IL-10+ compared to the VL group without stimulation and SLA restored the IL-10 in Treg. Additionally, an increase in Treg CD73+ in the VL group independently of stimuli compared to that in the NEC group was observed. We suggest that Treg are not the main source of IL-10, while the CD73 pathway may be an attempt to modulate the exacerbation of immune response in VL disease. Full article
(This article belongs to the Special Issue Advances in Cell Biology and Immunology of Leishmania)
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11 pages, 17886 KiB  
Article
Inhibiting Human and Leishmania Arginases Using Cannabis sativa as a Potential Therapy for Cutaneous Leishmaniasis: A Molecular Docking Study
by Aicha Assouab, Hajar El Filaly and Khadija Akarid
Trop. Med. Infect. Dis. 2022, 7(12), 400; https://doi.org/10.3390/tropicalmed7120400 - 26 Nov 2022
Cited by 2 | Viewed by 2486
Abstract
Cutaneous leishmaniasis (CL), a vector-borne parasitic disease caused by the Leishmania protozoan, is a serious public health problem in Morocco. The treatment of this disease is still based on pentavalent antimonials as the primary therapy, but these have associated side effects. Thus, the [...] Read more.
Cutaneous leishmaniasis (CL), a vector-borne parasitic disease caused by the Leishmania protozoan, is a serious public health problem in Morocco. The treatment of this disease is still based on pentavalent antimonials as the primary therapy, but these have associated side effects. Thus, the development of effective, risk-free alternative therapeutics based on natural compounds against leishmaniasis is urgent. Arginase, the key enzyme in the polyamine biosynthetic pathway, plays a critical role in leishmaniasis outcome and has emerged as a potential therapeutic target. The objective of this study was to test Cannabis sativa’s phytochemical components (cannabinoids and terpenoids) through molecular docking against Leishmania and human arginase enzymes. Our results showed that delta-9-tetrahydrocannabinol (THC) possessed the best binding energies of −6.02 and −6.35 kcal/mol with active sites of Leishmania and human arginases, respectively. Delta-9-THC interacted with Leishmania arginase through various amino acids including His139 and His 154 and linked to human arginase via His 126. In addition to delta-9-THC, caryophyllene oxide and cannabidiol (CBD) also showed a good inhibition of Leishmania and human arginases, respectively. Overall, the studied components were found to inhibit both arginases active sites via hydrogen bonds and hydrophobic interactions. These components may serve as therapeutic agents or in co-administrated therapy for leishmaniasis. Full article
(This article belongs to the Special Issue Advances in Cell Biology and Immunology of Leishmania)
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Review

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22 pages, 1610 KiB  
Review
Leishmaniasis: Immune Cells Crosstalk in Macrophage Polarization
by Fernanda Silva Almeida, Shayenne Eduarda Ramos Vanderley, Fernando Cézar Comberlang, Arthur Gomes de Andrade, Luiz Henrique Agra Cavalcante-Silva, Edson dos Santos Silva, Pedro Henrique de Sousa Palmeira, Ian P. G. do Amaral and Tatjana S. L. Keesen
Trop. Med. Infect. Dis. 2023, 8(5), 276; https://doi.org/10.3390/tropicalmed8050276 - 15 May 2023
Cited by 14 | Viewed by 4989
Abstract
Leishmaniasis is a complex infectious parasitic disease caused by protozoa of the genus Leishmania, belonging to a group of neglected tropical diseases. It establishes significant global health challenges, particularly in socio-economically disadvantaged regions. Macrophages, as innate immune cells, play a crucial role [...] Read more.
Leishmaniasis is a complex infectious parasitic disease caused by protozoa of the genus Leishmania, belonging to a group of neglected tropical diseases. It establishes significant global health challenges, particularly in socio-economically disadvantaged regions. Macrophages, as innate immune cells, play a crucial role in initiating the inflammatory response against the pathogens responsible for this disease. Macrophage polarization, the process of differentiating macrophages into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, is essential for the immune response in leishmaniasis. The M1 phenotype is associated with resistance to Leishmania infection, while the M2 phenotype is predominant in susceptible environments. Notably, various immune cells, including T cells, play a significant role in modulating macrophage polarization by releasing cytokines that influence macrophage maturation and function. Furthermore, other immune cells can also impact macrophage polarization in a T-cell-independent manner. Therefore, this review comprehensively examines macrophage polarization’s role in leishmaniasis and other immune cells’ potential involvement in this intricate process. Full article
(This article belongs to the Special Issue Advances in Cell Biology and Immunology of Leishmania)
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Other

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7 pages, 940 KiB  
Case Report
Visceral Leishmaniasis after Anti-Interleukin 17A (IL-17A) Therapy in a Patient Affected by Psoriatic Arthritis
by Tommaso Lupia, Silvia Corcione, Valentina Fornari, Barbara Rizzello, Roberta Bosio, Maria Teresa Brusa and Francesco Giuseppe De Rosa
Trop. Med. Infect. Dis. 2022, 7(10), 319; https://doi.org/10.3390/tropicalmed7100319 - 20 Oct 2022
Cited by 4 | Viewed by 1716
Abstract
The reactivation of latent Leishmania infection in chronic diseases and immunocompromised hosts is a broad and heterogeneous field in medicine and infectious diseases. We reported one of the first cases of Visceral Leishmaniasis occurring in a Caucasian middle-aged man living in an endemic [...] Read more.
The reactivation of latent Leishmania infection in chronic diseases and immunocompromised hosts is a broad and heterogeneous field in medicine and infectious diseases. We reported one of the first cases of Visceral Leishmaniasis occurring in a Caucasian middle-aged man living in an endemic country (Italy) for Leishmania infantum infection following secukinumab treatment for psoriatic arthritis. The patient was cured with a Liposomal Amphotericin B (L-AmB, 3 mg/Kg on days 1–5, followed by a dose on days 10, 17, 24, 31 and 38) regimen, after which his anti-interleukin 17 treatment was restarted—without recurrence in the follow-up. Full article
(This article belongs to the Special Issue Advances in Cell Biology and Immunology of Leishmania)
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