Leishmaniasis immunopathology—impact on design and use of vaccines, diagnostics and drugs

Kaye, Paul M.; Cruz, Israel; Picado, Albert; Bocxlaer, Katrien Van; Croft, Simon L.

doi:10.1007/s00281-020-00788-y

Cited by 56 publications

(55 citation statements)

References 162 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In leishmaniasis, this interaction assumes even greater complexity as the parasites reside within macrophages, established sentinels of our immune system. 18 Leishmania have developed several mechanisms to circumvent the microbicidal activity of macrophages by altering the expression of genes coding for cytokines, chemokines, transcription factors, membrane receptors and molecules involved in signal transduction, measurable by various high-throughput techniques, 19 thus providing important insights into the pathogenesis of VL.…”

Section: Re Sults and Discussionmentioning

confidence: 99%

Status of IL‐4 and IL‐10 driven markers in experimental models of Visceral Leishmaniasis

Moulik¹,

Karmakar

Joshi

et al. 2020

Parasite Immunology

View full text Add to dashboard Cite

Aim Leishmania donovani, the causative agent for visceral leishmaniasis (VL), modulates host monocytes/macrophages to ensure its survival. However, knowledge regarding the host‐parasite interactions underpinning the disease remains limited. As disease progression is associated with polarization of monocytes/macrophages towards M2, which is regulated by cytokines IL‐4/IL‐13 and IL‐10, this study evaluated the status of key IL‐4‐ and IL‐10 driven markers in experimental models of VL, as also evaluated their correlation, if any, with parasite load. Methods In liver and splenic tissues from L donovani–infected hamsters and BALB/c mice, the parasite burden was determined along with mRNA expression of IL‐4–driven markers, that is CD206, Arginase‐I, CCL17, CCL22, PPAR‐γ, STAT6, KLF4, FIZZ1 and YM1 along with IL‐10–driven markers, CXCL13, IL‐10, TGF‐β, VDR, CCR2 and CYP27A1. Results The mRNA expression of IL‐4‐ and IL‐10–driven markers was enhanced in both models, but only in the hamster model, the splenic tissues demonstrated a positive correlation between all the IL‐10–driven markers and parasite load. Conclusions Contrary to human VL, both models demonstrated an increased expression of IL‐4‐ and IL‐10–driven markers.

show abstract

Section: Re Sults and Discussionmentioning

confidence: 99%

Status of IL‐4 and IL‐10 driven markers in experimental models of Visceral Leishmaniasis

Moulik¹,

Karmakar

Joshi

et al. 2020

Parasite Immunology

View full text Add to dashboard Cite

show abstract

“…Determination of the cytokine profile in splenocytes showed high levels of IL-12 and IFN-γ and low levels of IL-4 and IL-10 in immunized groups, unlike high levels of IL-4 and IL-10 in control groups. In the BALB/c model, several lines of evidence suggest that the control of infection depends not only on the induction of IFN-γ-mediated responses but also on the control of IL-10 and IL-4 cytokines that are associated with pathology [ 59 , 60 ]. The immune response elicited by the His, AK, and His-AK groups conferred a significant reduction in parasite burden, especially in HisDTC-vaccinated mice.…”

Section: Discussionmentioning

confidence: 99%

Epitope Selection for Fighting Visceral Leishmaniosis: Not All Peptides Function the Same Way

et al. 2020

View full text Add to dashboard Cite

Visceral leishmaniosis (VL) caused by Leishmania infantum is a disease with an increasing prevalence worldwide. Treatments are expensive, toxic, and ineffective. Therefore, vaccination seems to be a promising approach to control VL. Peptide-based vaccination is a useful method due to its stability, absence of local side effects, and ease of scaling up. In this context, bioinformatics seems to facilitate the use of peptides, as this analysis can predict high binding affinity epitopes to MHC class I and II molecules of different species. We have recently reported the use of HisAK70 DNA immunization in mice to induce a resistant phenotype against L. major, L. infantum, and L. amazonensis infections. In the present study, we used bioinformatics tools to select promising multiepitope peptides (HisDTC and AK) from the polyprotein encoded in the HisAK70 DNA to evaluate their immunogenicity in the murine model of VL by L. infantum. Our results revealed that both multiepitope peptides were able to induce the control of VL in mice. Furthermore, HisDTC was able to induce a better cell-mediated immune response in terms of reduced parasite burden, protective cytokine profile, leishmanicidal enzyme modulation, and specific IgG2a isotype production in immunized mice, before and after infectious challenge. Overall, this study indicates that the HisDTC chimera may be considered a satisfactory tool to control VL because it is able to activate a potent CD4+ and CD8+ T-cell protective immune responses.

show abstract

“…Leishmania control has been based on preventing sand-fly bites, eliminating animal reservoirs (if it is zoonotic) and the early detection and effective treatment of cases in humans in the absence of an effective vaccine [93]. A key difference between VL and CL concerns Leishmania VL-causing species' tendency to cause systemic disease by invading macrophages in the liver, spleen and bone marrow whilst causing minimum damage to the skin [94].…”

Section: Leishmaniasismentioning

confidence: 99%

Loop-Mediated Isothermal Amplification as Point-of-Care Diagnosis for Neglected Parasitic Infections

Avendaño

Patarroyo

2020

IJMS

View full text Add to dashboard Cite

The World Health Organisation (WHO) has placed twenty diseases into a group known as neglected tropical diseases (NTDs), twelve of them being parasitic diseases: Chagas’ disease, cysticercosis/taeniasis, echinococcosis, food-borne trematodiasis, human African trypanosomiasis (sleeping sickness), leishmaniasis, lymphatic filariasis, onchocerciasis (river blindness), schistosomiasis, soil-transmitted helminthiasis (ascariasis, hookworm, trichuriasis), guinea-worm and scabies. Such diseases affect millions of people in developing countries where one of the main problems concerning the control of these diseases is diagnosis-based due to the most affected areas usually being far from laboratories having suitable infrastructure and/or being equipped with sophisticated equipment. Advances have been made during the last two decades regarding standardising and introducing techniques enabling diagnoses to be made in remote places, i.e., the loop-mediated isothermal amplification (LAMP) technique. This technique’s advantages include being able to perform it using simple equipment, diagnosis made directly in the field, low cost of each test and the technique’s high specificity. Using this technique could thus contribute toward neglected parasite infection (NPI) control and eradication programmes. This review describes the advances made to date regarding LAMP tests, as it has been found that even though several studies have been conducted concerning most NPI, information is scarce for others.

show abstract

Leishmaniasis immunopathology—impact on design and use of vaccines, diagnostics and drugs

Cited by 56 publications

References 162 publications

Status of IL‐4 and IL‐10 driven markers in experimental models of Visceral Leishmaniasis

Status of IL‐4 and IL‐10 driven markers in experimental models of Visceral Leishmaniasis

Epitope Selection for Fighting Visceral Leishmaniosis: Not All Peptides Function the Same Way

Loop-Mediated Isothermal Amplification as Point-of-Care Diagnosis for Neglected Parasitic Infections

Contact Info

Product

Resources

About