scholarly journals Sera from Visceral Leishmaniasis Patients Display Oxidative Activity and Affect the TNF-αProduction by MacrophagesIn Vitro

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Neci M. Soares ◽  
Joelma N. de Souza ◽  
Tatiana F. Leal ◽  
Eliana A. G. Reis ◽  
Maria S. Miranda ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Apolipoprotein A1 ◽  
Serum Factors ◽  
Effective Immune Response ◽  
The Matrix ◽  
Macrophage Stimulation ◽  
Necrosis Factor ◽  
Zoonotic Visceral Leishmaniasis

Mammalian protection against leishmanial infection depends on the development of an effective immune response. Zoonotic visceral leishmaniasis (ZVL) patients are usually unable to mount an effective immune response against the parasite and indeed appear to be severely immunosuppressed. This suppression has strong nonspecific and specific components mediated by serum factors and leishmanicidal activity of infected macrophages, respectively. The lipid profile has been shown to be altered in ZVL patients’ sera. This work aimed at (i) determining the HDL, Apo A1, LDL, and VLDL concentrations in ZVL patients’ sera; (ii) investigating the oxidative effect of ZVL patients’ sera on theβ-carotene matrix; (iii) measuring IL-10, IL-6, IL-12p40, and tumour necrosis factor-α(TNF-α) concentrations in the macrophage cultures, to which 10% of ZVL patients’ serum had been added. Levels of HDL, LDL fraction, and apolipoprotein A1 in ZVL patients’ sera were lower than those of healthy individuals’ sera, except for the mean level of VLDL. The matrix ofβ-carotene and linoleic acid system was oxidized in the presence of ZLV patients’ sera. The presence of ZVL patients’ sera did not modify the cytokine production of IL-6, IL-12p40, and IL-10 by human macrophagesin vitrobut TNF-αproduction was altered, probably due to lack of macrophage stimulation by lipoprotein.

scholarly journals SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma

2020 ◽  
Author(s):  
Emanuele Andreano ◽  
Giulia Piccini ◽  
Danilo Licastro ◽  
Lorenzo Casalino ◽  
Nicole V. Johnson ◽  
...  
Keyword(s):  
South Africa ◽  
Immune Response ◽  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Receptor Binding Domain ◽  
The United Kingdom ◽  
Effective Immune Response ◽  
Recent Emergence ◽  
Natural Variants

ABSTRACTTo investigate the evolution of SARS-CoV-2 in the immune population, we co-incubated authentic virus with a highly neutralizing plasma from a COVID-19 convalescent patient. The plasma fully neutralized the virus for 7 passages, but after 45 days, the deletion of F140 in the spike N-terminal domain (NTD) N3 loop led to partial breakthrough. At day 73, an E484K substitution in the receptor-binding domain (RBD) occurred, followed at day 80 by an insertion in the NTD N5 loop containing a new glycan sequon, which generated a variant completely resistant to plasma neutralization. Computational modeling predicts that the deletion and insertion in loops N3 and N5 prevent binding of neutralizing antibodies. The recent emergence in the United Kingdom and South Africa of natural variants with similar changes suggests that SARS-CoV-2 has the potential to escape an effective immune response and that vaccines and antibodies able to control emerging variants should be developed.One Sentence SummaryThree mutations allowed SARS-CoV-2 to evade the polyclonal antibody response of a highly neutralizing COVID-19 convalescent plasma.

scholarly journals Effect of immunosuppressants on the parasite load developed in, and immune response to, visceral leishmaniasis: A comparative study in a mouse model

2021 ◽  
Vol 15 (2) ◽  
pp. e0009126
Author(s):  
Lorena Bernardo ◽  
Jose Carlos Solana ◽  
Alba Romero-Kauss ◽  
Carmen Sánchez ◽  
Eugenia Carrillo ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Tumour Necrosis ◽  
Parasite Load ◽  
Th1 Cells ◽  
Infection Period ◽  
Immunosuppressed Patients ◽  
Necrosis Factor ◽  
Immunosuppressant Treatment

The increasing use of immunosuppressants in areas where visceral leishmaniasis (VL) is endemic has increased the number of people susceptible to developing more severe forms of the disease. Few studies have examined the quality of the immune response in immunosuppressed patients or experimental animals with VL. The present work characterises the parasite load developed in, and immune response to, Leishmania infantum-induced VL in C57BL/6 mice that, prior to and during infection, received immunosuppressant treatment with methylprednisolone (MPDN), anti-tumour necrosis factor (anti-TNF) antibodies, or methotrexate (MTX). The latter two treatments induced a significant reduction in the number of CD4+ T lymphocytes over the infection period. The anti-TNF treatment was also associated with a higher parasite load in the liver and a lower parasite load in the spleen. This, plus a possibly treatment-induced reduction in the number of cytokine-producing Th1 cells in the spleen, indicates the development of more severe VL. Interestingly, the MPDN and (especially) MTX treatments provoked a greater presence of soluble Leishmania antigen-specific multi-cytokine-producing T cells in the spleen and a lower liver parasite load than in control animals. These results highlight the need to better understand how immunosuppressant treatments might influence the severity of VL in human patients.

scholarly journals Combined in vitro IL-12 and IL-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis

2020 ◽  
Vol 14 (1) ◽  
pp. e0008021 ◽  
Author(s):  
Sidnei Ferro Costa ◽  
Vinícius Oliveira Gomes ◽  
Marilene Oliveira dos Santos Maciel ◽  
Larissa Martins Melo ◽  
Gabriela Lovizutto Venturin ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Cellular Immune Response ◽  
Cellular Immune

scholarly journals Zoonotic Visceral Leishmaniasis: New Insights on Innate Immune Response by Blood Macrophages and Liver Kupffer Cells to Leishmania infantum Parasites

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 100
Author(s):  
Armanda Viana Rodrigues ◽  
Ana Valério-Bolas ◽  
Graça Alexandre-Pires ◽  
Maria Aires-Pereira ◽  
Telmo Nunes ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Innate Immune Response ◽  
Kupffer Cells ◽  
Immune Activation ◽  
Innate Immune ◽  
Host Cells ◽  
Leishmania Infection ◽  
Phagocytic Cells ◽  
Zoonotic Visceral Leishmaniasis

L. infantum is the aetiological agent of zoonotic visceral leishmaniasis (ZVL), a disease that affects humans and dogs. Leishmania parasites are well adapted to aggressive conditions inside the phagolysosome and can control the immune activation of macrophages (MØs). Although MØs are highly active phagocytic cells with the capacity to destroy pathogens, they additionally comprise the host cells for Leishmania infection, replication, and stable establishment in the mammal host. The present study compares, for the first time, the innate immune response to L. infantum infection of two different macrophage lineages: the blood macrophages and the liver macrophages (Kupffer cells, KC). Our findings showed that L. infantum takes advantage of the natural predisposition of blood-MØs to phagocyte pathogens. However, parasites rapidly subvert the mechanisms of MØs immune activation. On the other hand, KCs, which are primed for immune tolerance, are not extensively activated and can overcome the dormancy induced by the parasite, exhibiting a selection of immune mechanisms, such as extracellular trap formation. Altogether, KCs reveal a different pattern of response in contrast with blood-MØs when confronting L. infantum parasites. In addition, KCs response appears to be more efficient in managing parasite infection, thus contributing to the ability of the liver to naturally restrain Leishmania dissemination.

scholarly journals Modulation of the immune response and infection pattern to Leishmania donovani in visceral leishmaniasis due to arsenic exposure: An in vitro study

PLoS ONE ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. e0210737 ◽  
Author(s):  
Ghufran Ahmed ◽  
Ajit K. Thakur ◽  
Pushpanjali ◽  
Snehil ◽  
Sanjay K. Chaturvedi ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Arsenic Exposure ◽  
In Vitro Study ◽  
Vitro Study ◽  
Infection Pattern

Synergic effect of eugenol oleate with amphotericin B augments anti-leishmanial immune response in experimental visceral leishmaniasis in vitro and in vivo

2021 ◽  
Vol 91 ◽  
pp. 107291
Author(s):  
Amrita Kar ◽  
Adithyan Jayaraman ◽  
Mamilla R Charan Raja ◽  
Sujatha Srinivasan ◽  
Joy Debnath ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Amphotericin B ◽  
Synergic Effect

Lupeol induces immunity and protective efficacy in a murine model against visceral leishmaniasis

Parasitology ◽  
2019 ◽  
Vol 146 (11) ◽  
pp. 1440-1450 ◽  
Author(s):  
Gurpreet Kaur ◽  
Kalpana Chauhan ◽  
Sukhbir Kaur
Keyword(s):  
Nitric Oxide ◽  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Protective Efficacy ◽  
Parasite Burden ◽  
Delayed Type Hypersensitivity ◽  
Reference Drug ◽  
Th2 Immune Response

AbstractThe available chemotherapeutics for the cure of visceral leishmaniasis (VL) are linked with many detrimental effects. Moreover, VL is associated with the suppression of protective Th1 immune response of the host and induction of disease exaggerating Th2 immune response. Therefore, there is an urgent requirement of therapeutics which can augment the immune status of the host to cure this disease. In the current investigation, the antileishmanial potential of lupeol was monitored in vitro and in vivo in inbred BALB/c mice against Leishmania donovani. Lupeol showed potent antipromastigote activity via arresting parasites at sub G0/G1 phase in vitro. Lupeol significantly decreased the splenic parasite burden by inducing strong delayed-type hypersensitivity responses in contrary to untreated infected animals. The therapeutic efficacy of lupeol was observed to be similar to the reference drug, AmB. Treatment of infected animals with lupeol depicted enhanced levels of T cells and Th1 cytokines in contrast to only infected controls. Further lupeol treatment upregulated the levels of nuclear factor κ B and nitric oxide synthase genes and elevated the production of reactive oxygen species and nitric oxide. Unlike AmB, lupeol-treated infected animals did not show any toxicity. These findings are promising and indicate that lupeol can serve as a prototype drug for the cure of VL.

scholarly journals Synergistic activation of NF-kappaB by tumor necrosis factor alpha and gamma interferon via enhanced I kappaB alpha degradation and de novo I kappaBbeta degradation.

1997 ◽  
Vol 17 (11) ◽  
pp. 6746-6754 ◽  
Author(s):  
J L Cheshire ◽  
A S Baldwin
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Ifn Gamma ◽  
Effective Immune Response ◽  
Factor Alpha ◽  
Nf Kappab ◽  
Necrosis Factor

Tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) are required for an effective immune response to bacterial infection and these cytokines synergize in a variety of biological responses, including the induction of cytokine, cell adhesion, and inducible nitrous oxide synthase gene expression. Typically, the synergistic effect on gene expression is due to the independent activation of nuclear factor kappaB (NF-kappaB) by TNF-alpha and of signal transducers and activators of transcription or IFN-regulatory factor 1 by IFNs, allowing these transcription factors to bind their unique promoter sites. However, since activation of NF-kappaB by TNF-alpha is often transient and would not activate long-term kappaB-dependent transcription effectively, we explored the effects of IFN-gamma on TNF-alpha-induced NF-kappaB activity. IFN-gamma, which typically does not activate NF-kappaB, synergistically enhanced TNF-alpha-induced NF-kappaB nuclear translocation via a mechanism that involves the induced degradation of I kappaBbeta and that apparently requires tyrosine kinase activity in preneuronal cells but not in endothelial cells. Correspondingly, cotreatment of cells with TNF-alpha and IFN-gamma leads to persistent activation of NF-kappaB and to potent activation of kappaB-dependent gene expression, which may explain, at least in part, the synergy observed between these cytokines, as well as their involvement in the generation of an effective immune response.

scholarly journals Intranasal vaccine from whole Leishmania donovani antigens provides protection and induces specific immune response against visceral leishmaniasis

2021 ◽  
Vol 15 (8) ◽  
pp. e0009627
Author(s):  
Doumet Georges Helou ◽  
Aurélie Mauras ◽  
François Fasquelle ◽  
Juliane Sousa Lanza ◽  
Philippe M. Loiseau ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Parasite Clearance ◽  
Effective Vaccine ◽  
Vaccine Strategy ◽  
Intranasal Route ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

Visceral leishmaniasis is a protozoan disease associated with high fatality rate in developing countries. Although the drug pipeline is constantly improving, available treatments are costly and live-threatening side effects are not uncommon. Moreover, an approved vaccine against human leishmaniasis does not exist yet. Using whole antigens from Leishmania donovani promastigotes (LdAg), we investigated the protective potential of a novel adjuvant-free vaccine strategy. Immunization of mice with LdAg via the intradermal or the intranasal route prior to infection decreases the parasitic burden in primary affected internal organs, including the liver, spleen, and bone marrow. Interestingly, the intranasal route is more efficient than the intradermal route, leading to better parasite clearance and remarkable induction of adaptive immune cells, notably the helper and cytotoxic T cells. In vitro restimulation experiments with Leishmania antigens led to significant IFN-γ secretion by splenocytes; therefore, exemplifying specificity of the adaptive immune response. To improve mucosal delivery and the immunogenic aspects of our vaccine strategy, we used polysaccharide-based nanoparticles (NP) that carry the antigens. The NP-LdAg formulation is remarkably taken up by dendritic cells and induces their maturation in vitro, as revealed by the increased expression of CD80, CD86 and MHC II. Intranasal immunization with NP-LdAg does not improve the parasite clearance in our experimental timeline; however, it does increase the percentage of effector and memory T helper cells in the spleen, suggesting a potential induction of long-term memory. Altogether, this study provides a simple and cost-effective vaccine strategy against visceral leishmaniasis based on LdAg administration via the intranasal route, which could be applicable to other parasitic diseases.

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