Immunoprotective responses of T helper type 1 stimulatory protein-S-adenosyl-L-homocysteine hydrolase against experimental visceral leishmaniasis

Khare, Prashant; Jaiswal, Anil K.; Tripathi, Chandra Dev Pati; Sundar, Shyam; Dube, Anuradha

doi:10.1111/cei.12780

Cited by 10 publications

(10 citation statements)

References 51 publications

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“…Since the identification of various subsets of helper T cells (Th1, Th2, Th9, Th17, Th22, Treg and Tfh cells), their functions have been examined in different inflammatory diseases including leishmaniasis. Exploring Th subsets contribution in leishmaniasis revealed that the disease progression was associated with the up‐regulation of Th2 and Treg cells responses by producing anti‐inflammatory cytokines IL‐10 and TGF‐β 23 while disease regression was related to the activation of Th17 and Th1 cells producing various pro‐inflammatory cytokines, for example IL‐17 and IFN‐γ 30,31 . Among Th subsets, IL‐9 producing CD4+ T cells are characterized based on the production of IL‐9, 32 and their associations and functions in VL remain to be clear.…”

Section: Discussionmentioning

confidence: 99%

Treatment effects on IL‐9+CD4+ T cells and the cytokines influencing IL‐9 production in paediatric visceral leishmaniasis

Moravej

Choopanizadeh

Pourabbas

et al. 2020

Parasite Immunology

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IL-9 + CD4+T cells comprise a heterogeneous population of T cells including T helper (Th)-2, 1 Th17, 2 regulatory T cells 3 and a recently discovered T-cell subset named Th9. 4 Closely related to Th2, Th9 is deviated from naïve CD4+ T cells in the presence of transforming growth factor (TGF)-β, interleukin (IL)-4, IL-21, tumour necrosis factor (TNF)-α and IL-10. 5-8 Although IL-9 is known as prototype cytokine of Th9, these cells cannot produce other cytokines such as IL-4, IL-5, IL-13 and interferon (IFN)-γ. 9 To produce IL-9, several cytokines (IL-1α/β, IL-2, IFN-α and IL-33) are considered as the activators, 5 and on the other hand, interferon (IFN)-γ is reported to play inhibitory effects on Th9 differentiation and IL-9 production both in vitro and in vivo. 10 Collectively, as shown in Figure 1, various cytokines are involved in the differentiation of IL-9 + CD4+T cells as well as IL-9 secretion. Although the role of IL-9 + CD4+T cells and its prominent cytokine, IL-9, has been clarified in the autoimmune diseases, 11 allergic diseases 12,13 and tumours, 14 limited studies have investigated its role in the infectious diseases. Leishmaniasis, as an infectious disease, is caused by obligatory intracellular protozoan parasite belonging to the genus Leishmania (L). Based on the Leishmania species, host genetics, interaction between host immune system and parasites and the load of Leishmania entrance, the clinical manifestations of the disease range from self-healing cutaneous leishmaniasis (CL) to life-threatening form of visceral leishmanisis (VL)

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Section: Discussionmentioning

confidence: 99%

Treatment effects on IL‐9+CD4+ T cells and the cytokines influencing IL‐9 production in paediatric visceral leishmaniasis

Moravej

Choopanizadeh

Pourabbas

et al. 2020

Parasite Immunology

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“…The infective insect stage-specific protein expressed by gene META1 is specific to infective metacyclic promastigotes . Interestingly, the enzyme adenosylhomocysteinase, involved in amino-acid biosynthesis (synthesis of l -homocysteine from S -adenosyl- l -homocysteine), was found to be highly abundant, which is expected for Leishmania promastigotes, and it has also been shown to be immunogenic in hamsters and human PBMC stimulation assays . The uncharacterized protein A4H3U0, identified among the most abundant proteins, is in fact the most abundant in the L.…”

Section: Discussionmentioning

confidence: 83%

“…79 Interestingly, the enzyme adenosylhomocysteinase, involved in amino-acid biosynthesis (synthesis of L-homocysteine from Sadenosyl-L-homocysteine), was found to be highly abundant, which is expected for Leishmania promastigotes, and it has also been shown to be immunogenic in hamsters and human PBMC stimulation assays. 80 The uncharacterized protein A4H3U0, identified among the most abundant proteins, is in fact the most abundant in the L. braziliensis secretome. This protein is predicted to have a metalloendopeptidase activity with known cell adhesion functions and could be analyzed further as a potential virulence factor and antigen candidate.…”

Section: ■ Discussionmentioning

confidence: 99%

Proteomic Analysis of the Promastigote Secretome of Seven Leishmania Species

et al. 2021

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Leishmaniasis is one of the most impactful parasitic diseases worldwide, endangering the lives of 1 billion people every year. There are 20 different species of Leishmania able to infect humans, causing cutaneous (CL), visceral (VL), and/or mucocutaneous leishmaniasis (MCL). Leishmania parasites are known to secrete a plethora of proteins to establish infection and modulate the host's immune system. In this study, we analyzed using tandem mass spectrometry the total protein content of the secretomes produced by promastigote forms from seven Leishmania species grown in serum-free in vitro cultures. The core secretome shared by all seven Leishmania species corresponds to up to one-third of total secreted proteins, suggesting conserved mechanisms of adaptation to the vertebrate host. The relative abundance confirms the importance of known virulence factors and some proteins uniquely present in CL-or VL-causing species and may provide further insight regarding their pathogenesis. Bioinformatic analysis showed that most proteins were secreted via unconventional mechanisms, with an important role for vesiclebased secretion for all species. Gene Ontology annotation and enrichment analyses showed a high level of functional conservation among species. This study contributes to the current knowledge on the biological significance of differently secreted proteins and provides new information on the correlation of Leishmania secretome to clinical outcomes and species-specific pathogenesis.

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“…Multiple enzymes of the glycolytic pathway like aldolase, enolase, triose phosphate isomerase, etc. are being targeted to develop vaccines against VL [59], [155]. Still, these studies warrant more clinical data.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple enzymes of the glycolytic pathway such as enolase, aldolase, are recognized as potential Th1 stimulatory proteins in PBMCs from Leishmania infected hamsters and leishmaniasis patients [56], [57]. Because the host T-cell responses are critical in managing VL, these Leishmania proteins that kindle the host T-cell response can be considered to be effective vaccine and drug targets [58], [59].…”

Section: Purine Salvage Pathwaymentioning

confidence: 99%

Metabolic Pathways of Leishmania Parasite: Source of Pertinent Drug Targets and Potent Drug Candidates

Jain¹,

Sahu²,

Kumar³

2022

Preprint

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Leishmaniasis is a tropical disease caused by a protozoan parasite Leishmania that is transmitted via infected female sandflies. At present, leishmaniasis treatment mainly counts on chemotherapy. The currently available drugs against leishmaniasis are costly, toxic, with multiple side effects, and limitations in the administration route. The rapid emergence of drug resistance has severely reduced the potency of anti-leishmanial drugs. As a result, there is a pressing need for the development of novel anti-leishmanial drugs with high potency, low cost, acceptable toxicity, and good pharmacokinetics features. Due to the availability of preclinical data, drug repurposing is a valuable approach for speeding up the development of effective antileishmanial through pointing to new drug targets in less time having low costs and risk. Metabolic pathways of this parasite play a crucial role in the growth and proliferation of Leishmania species during the various stages of their life cycle. Based on available genomics/proteomics information, known pathways-based (sterol biosynthetic pathway, purine salvage pathway, glycolysis, GPI biosynthesis, hypusine, polyamine biosynthesis) Leishmania-specific proteins could be targeted with known drugs that were used in other diseases, resulting in finding new promising anti-leishmanial therapeutics. The present review discusses various metabolic pathways of the Leishmania parasite and some drug candidates targeting these pathways effectively that could be potent drugs against leishmaniasis in the future.

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Immunoprotective responses of T helper type 1 stimulatory protein-S-adenosyl-L-homocysteine hydrolase against experimental visceral leishmaniasis

Cited by 10 publications

References 51 publications

Treatment effects on IL‐9+CD4+ T cells and the cytokines influencing IL‐9 production in paediatric visceral leishmaniasis

Treatment effects on IL‐9+CD4+ T cells and the cytokines influencing IL‐9 production in paediatric visceral leishmaniasis

Proteomic Analysis of the Promastigote Secretome of Seven Leishmania Species

Metabolic Pathways of Leishmania Parasite: Source of Pertinent Drug Targets and Potent Drug Candidates

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