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Special Issue "Host-Pathogen Interactions During Leishmania Infections—A Special Issue in Honor of Prof. Dr. John David"

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

Deadline for manuscript submissions: 30 September 2023 | Viewed by 2680

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Prof. Dr. Jeffrey Jon Shaw

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Guest Editor

Instituto de Ciencias Biomédicas, Universidade de São Paulo, Sao Paulo, Brazil
Interests: biological sciences; collective health; ecology; health sciences; parasitology

Prof. Dr. Abhay Satoskar

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Guest Editor

Department of Microbiology, The Ohio State University, Columbus, OH 43210, USA
Interests: parasitic diseases; leishmaniasis; immunology; vaccines
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Dear Colleagues,

John R. David graduated in Medicine in Chicago and joined the house staff of the Massachusetts General Hospital in Boston, moving to New York University where he discovered the macrophage migration inhibitory factor (MIF) in the mid-1960s. This monumental discovery opened the door to understanding how macrophages communicate. From there, he went to Harvard where he made ground-breaking contributions in the early 1970s on the function of cytokines in allergies. He sensed the gap between technical advances and tropical medicine and dedicated his forces to closing it, especially in leishmaniasis. This began with the production of the first leishmanial-specific monoclonal antibodies in the 1980s with Diana McMahon-Pratt. Latterly, he established a long-term collaborative project between Harvard and Brazil on the disease. He also sensed the need for simpler, less aggressive methods of treatment and personally pioneered the use of radiofrequency-induced heat therapy for cutaneous leishmaniasis in the Middle East and South America. Under his guidance, research in tropical diseases at the Harvard Medical School flourished, and upon his retirement, he became the Richard Pearson Strong Emeritus Professor of Tropical Public Health in the Harvard Faculty of Public Health. John’s enthusiasm has no limits and is contagious, as can be seen by the trail of discoveries that his work has led to. This Special Issue is in honour of John’s amazing contributions, with a focus on the many fields of neglected pathological diseases.

Prof. Dr. Jeffrey Jon Shaw
Prof. Dr. Abhay Satoskar
Guest Editors

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Keywords

leishmaniasis
prevention
pathology
cytokines
macrophages
vaccination
parasite diversity
treatment
genomics
transmission

Published Papers (5 papers)

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Open AccessArticle

Potential Biomarkers for Asymptomatic Visceral Leishmaniasis among Iraq-Deployed U.S. Military Personnel

Fernanda Fortes de Araujo

and

Pathogens 2023, 12(5), 705; https://doi.org/10.3390/pathogens12050705 - 12 May 2023

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Abstract

Visceral leishmaniasis (VL) is a chronic infection caused by Leishmania (L.) donovani or L. infantum parasites. Despite having the infection, most individuals never develop the clinical disease and are able to control the parasite and remain asymptomatic. However, some progress to symptomatic VL, leading to death if untreated. The host immune response has a major role in determining the progression and severity of the clinical manifestations in VL; several immune biomarkers of symptomatic VL have been described with interferon-gamma release as a surrogate biomarker of host cellular immunity. However, new biomarkers to identify asymptomatic VL (AVL) are needed for the identification of people at risk for VL activation. In our study, levels of chemokine/cytokine in the supernatants of peripheral mononuclear blood cells (PBMC) from 35 AVL⁺ Iraq-deployed participants, stimulated in vitro with soluble Leishmania antigen for 72 h, were assessed by a bead-based assay that allows the measurement of multiple analytes. PBMC of AVL-negative military beneficiaries were used as controls. Monocyte Chemoattractant Protein-1, Monokine Induced by Gamma Interferon and Interleukin-8, were detected at high levels in AVL⁺ stimulated cultures from Iraq deployers compared to uninfected controls. Measurement of chemokine/cytokine levels can identify cellular immune responses in AVL⁺ asymptomatic individuals. Full article

(This article belongs to the Special Issue Host-Pathogen Interactions During Leishmania Infections—A Special Issue in Honor of Prof. Dr. John David)

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Open AccessArticle

Infectiousness of Asymptomatic Meriones shawi, Reservoir Host of Leishmania major

Kamal Eddine Benallal

Nalia Mekarnia

Zoubir Harrat

and

Petr Volf

Pathogens 2023, 12(4), 614; https://doi.org/10.3390/pathogens12040614 - 18 Apr 2023

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Abstract

Leishmaniases are neglected diseases caused by protozoans of the genus Leishmania that threaten millions of people worldwide. Cutaneous leishmaniasis (CL) caused by L. major is a typical zoonosis transmitted by phlebotomine sand flies and maintained in rodent reservoirs. The female sand fly was assumed to become infected by feeding on the skin lesion of the host, and the relative contribution of asymptomatic individuals to disease transmission was unknown. In this study, we infected 32 Meriones shawi, North African reservoirs, with a natural dose of L. major obtained from the gut of infected sand flies. Skin manifestations appeared in 90% of the animals, and xenodiagnosis with the proven vector Phlebotomus papatasi showed transmissibility in 67% of the rodents, and 45% were repeatedly infectious to sand flies. Notably, the analysis of 113 xenodiagnostic trials with 2189 sand flies showed no significant difference in the transmissibility of animals in the asymptomatic and symptomatic periods; asymptomatic animals were infectious several weeks before the appearance of skin lesions and several months after their healing. These results clearly confirm that skin lesions are not a prerequisite for vector infection in CL and that asymptomatic animals are an essential source of L. major infection. These data are important for modeling the epidemiology of CL caused by L. major. Full article

(This article belongs to the Special Issue Host-Pathogen Interactions During Leishmania Infections—A Special Issue in Honor of Prof. Dr. John David)

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Open AccessArticle

Leishmania Infection-Induced Proteolytic Processing of SIRPα in Macrophages

and

Pathogens 2023, 12(4), 593; https://doi.org/10.3390/pathogens12040593 - 13 Apr 2023

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Abstract

The shedding of cell surface receptors may bring synergistic outcomes through the loss of receptor-mediated cell signaling and competitive binding of the shed soluble receptor to its ligand. Thus, soluble receptors have both biological importance and diagnostic importance as biomarkers in immunological disorders. Signal regulatory protein α (SIRPα), one of the receptors responsible for the ‘don’t-eat-me’ signal, is expressed by myeloid cells where its expression and function are in part regulated by proteolytic cleavage. However, reports on soluble SIRPα as a biomarker are limited. We previously reported that mice with experimental visceral leishmaniasis (VL) manifest anemia and enhanced hemophagocytosis in the spleen accompanied with decreased SIRPα expression. Here, we report increased serum levels of soluble SIRPα in mice infected with Leishmania donovani, a causative agent of VL. Increased soluble SIRPα was also detected in a culture supernatant of macrophages infected with L. donovani in vitro, suggesting the parasite infection promotes ectodomain shedding of SIRPα on macrophages. The release of soluble SIRPα was partially inhibited by an ADAM proteinase inhibitor in both LPS stimulation and L. donovani infection, suggesting a shared mechanism for cleavage of SIRPα in both cases. In addition to the ectodomain shedding of SIRPα, both LPS stimulation and L. donovani infection induced the loss of the cytoplasmic region of SIRPα. Although the effects of these proteolytic processes or changes in SIRPα still remain unclear, these proteolytic regulations on SIRPα during L. donovani infection may explain hemophagocytosis and anemia induced by infection, and serum soluble SIRPα may serve as a biomarker for hemophagocytosis and anemia in VL and the other inflammatory disorders. Full article

(This article belongs to the Special Issue Host-Pathogen Interactions During Leishmania Infections—A Special Issue in Honor of Prof. Dr. John David)

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Open AccessArticle

Toll-like Receptor-9 (TLR-9) Signaling Is Crucial for Inducing Protective Immunity following Immunization with Genetically Modified Live Attenuated Leishmania Parasites

and

Pathogens 2023, 12(4), 534; https://doi.org/10.3390/pathogens12040534 - 29 Mar 2023

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Abstract

No human vaccine is available for visceral leishmaniasis (VL). Live attenuated centrin gene-deleted L. donovani (LdCen^−/−) parasite vaccine has been shown to induce robust innate immunity and provide protection in animal models. Toll-like receptors (TLRs) are expressed in innate immune cells and are essential for the early stages of Leishmania infection. Among TLRs, TLR-9 signaling has been reported to induce host protection during Leishmania infection. Importantly, TLR-9 ligands have been used as immune enhancers for non-live vaccination strategies against leishmaniasis. However, the function of TLR-9 in the generation of a protective immune response in live attenuated Leishmania vaccines remains unknown. In this study, we investigated the function of TLR-9 during LdCen^−/− infection and found that it increased the expression of TLR-9 on DCs and macrophages from ear-draining lymph nodes and spleen. The increase in TLR-9 expression resulted in changes in downstream signaling in DCs mediated through signaling protein myeloid differentiation primary response 88 (MyD88), resulting in activation and nuclear translocation of nuclear factor-κB (NF-κB). This process resulted in an increase in the DC’s proinflammatory response, activation, and DC-mediated CD4⁺T cell proliferation. Further, LdCen^−/− immunization in TLR-9^−/− mice resulted in a significant loss of protective immunity. Thus, LdCen^−/− vaccine naturally activates the TLR-9 signaling pathway to elicit protective immunity against virulent L. donovani challenge. Full article

(This article belongs to the Special Issue Host-Pathogen Interactions During Leishmania Infections—A Special Issue in Honor of Prof. Dr. John David)

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Leishmaniosis in Greece: The Veterinary Perspective

Isaia Symeonidou

Georgios Sioutas

Athanasios I. Gelasakis

Constantina N. Tsokana

and

Elias Papadopoulos

Pathogens 2023, 12(6), 769; https://doi.org/10.3390/pathogens12060769 - 26 May 2023

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Abstract

Leishmaniosis caused by the protozoon Leishmania infantum that is transmitted through the bites of infected phlebotomine sandflies is of major veterinary concern in Greece. The country is endemic with particularly favourable environmental conditions for the spread of this infection. Moreover, Greece remains a popular touristic destination, and the continuous travel of pets raises concern regarding the possible dissemination of infection from endemic to non-endemic areas. Dogs are the main reservoir host, although other animal species, including humans, may also be infected. Canine leishmaniosis manifests as a visceral disease that can result in death if left untreated. Serological and molecular epizootiological studies have confirmed circulation of the parasite in Greek canine and feline populations as well as in other mammals. As a result, constant surveillance and identification of high-risk localities are necessary to establish chemoprophylactic protocols for travelling animals to safeguard animal and public health. Full article

(This article belongs to the Special Issue Host-Pathogen Interactions During Leishmania Infections—A Special Issue in Honor of Prof. Dr. John David)

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Special Issue "Host-Pathogen Interactions During Leishmania Infections—A Special Issue in Honor of Prof. Dr. John David"

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