Immunochemotherapy for visceral leishmaniasis: Combinatorial action of Miltefosine plus LBSapMPL vaccine improves adaptative Th1 immune response with control of splenic parasitism in experimental hamster model

SUMMARYIn South America, visceral leishmaniasis is frequently caused byLeishmania infantumand, at an unknown frequency, byLeishmania amazonensis. Therefore, mixed infections with these organisms are possible. Mixed infections might affect the clinical course, immune response, diagnosis, treatment and epidemiology of the disease. Here we describe the clinical course of mixed infections withL. amazonensisandL. infantumin a hamster model. We show that mixed infections are associated with more severe clinical disease than infection withL. amazonensisorL. infantumalone. In spleens with mixed infections,L. infantumoutcompetedL. amazonensisin the tissue, but not in culture from tissue. We found increased levels of IgG in animals infected withL. infantum.Although more than 30 bands were revealed in a Western blot, the highest immunogenicity was observed with proteins having molecular masses of 95 and 90 kDa, whereas proteins with molecular masses of lower than 50 kDa were reactive frequently with serum from hamsters infected withL. amazonensis, and proteins with molecular masses of 80 and 70 kDa were reactive only with serum from hamsters infected withL. infantum. This finding has important implications regarding the biology ofLeishmaniaand humoral immune responses to infections with these organisms.

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Leishmaniasis: A new method for confirming cure and detecting asymptomatic infection in patients receiving immunosuppressive treatment for autoimmune disease

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009662 ◽

2021 ◽

Vol 15 (8) ◽

pp. e0009662

Author(s):

Laura Botana ◽

Ana Victoria Ibarra-Meneses ◽

Carmen Sanchez ◽

Belen Matia ◽

Juan Victor San Martin ◽

...

Keyword(s):

Immune Response ◽

Autoimmune Disease ◽

Visceral Leishmaniasis ◽

Immunosuppressive Treatment ◽

Asymptomatic Infection ◽

Cytokine Release ◽

Peripheral Blood Mononuclear ◽

Th1 Immune Response ◽

Risk Of Relapse ◽

Stimulation Of

Visceral leishmaniasis (VL) in patients receiving immunosuppressant drugs for autoimmune disease has been on the rise. It is important—but difficult—to know when cure has been achieved in these patients since the withdrawal of immunosuppressants during antileishmania treatment is commonly required, and there is a risk of relapse when immunosuppression is restored. The prevalence of asymptomatic infection among those immunosuppressed for autoimmune disease is also uncertain. The present work describes how cytokine release assays can be used to confirm the cure of VL, and to determine the prevalence of asymptomatic infection, in such patients. After collection of blood from volunteers (n = 108), SLA-stimulation of peripheral blood mononuclear cell cultures and of whole blood was found to induce the production of different combinations of cytokines that served to confirm recovery from VL, and asymptomatic Leishmania infection. Indeed, cure was confirmed in 14 patients, all of whom showed a specific Th1 immune response against Leishmania, and the prevalence of asymptomatic infection was determined as 21.27%. Cytokine profiles could be used to manage VL in patients with autoimmune disease, and to identify and better protect those with asymptomatic infection who are at risk of developing this disease.

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Protein Malnutrition Impairs the Immune Response and Influences the Severity of Infection in a Hamster Model of Chronic Visceral Leishmaniasis

PLoS ONE ◽

10.1371/journal.pone.0089412 ◽

2014 ◽

Vol 9 (2) ◽

pp. e89412 ◽

Cited By ~ 14

Author(s):

Eugenia Carrillo ◽

Mª Angeles Jimenez ◽

Carmen Sanchez ◽

Joana Cunha ◽

Camila Marinelli Martins ◽

...

Keyword(s):

Immune Response ◽

Visceral Leishmaniasis ◽

Protein Malnutrition ◽

Hamster Model

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Biological Underpinnings of Health Alterations in Women With PTSD: A Sex Disparity

Biological Research For Nursing ◽

10.1177/1099800405276709 ◽

2005 ◽

Vol 7 (1) ◽

pp. 44-54 ◽

Cited By ~ 22

Author(s):

Jessica M. Gill ◽

Sarah L. Szanton ◽

Gayle G. Page

Keyword(s):

Posttraumatic Stress Disorder ◽

Immune Response ◽

Major Depressive Disorder ◽

Stress Disorder ◽

Neuroendocrine System ◽

Major Depressive ◽

Fourfold Increase ◽

Sex Disparity ◽

Th1 Immune Response

Women develop posttraumatic stress disorder (PTSD) at twice the rate of men, even though fewer women than men experience traumatic events over their lifetimes. Current studies of individuals with PTSD provide evidence of alterations in the neuroendocrine system that involve levels and activity of cortisol and DHEA and changes in immune function that predispose these individuals toward an innate (Th1) immune response. Yet few studies have addressed the possible role of these biologic alterations in women’s increased vulnerability to developing PTSD. In addition, current studies are limited in their ability to link biologic alterations to the observed fourfold increase in medical conditions in women with PTSD as compared to women without PTSD. And finally, few studies have addressed the biologic impact of co-occurring major depressive disorder (MDD) in individuals with PTSD. This critical review provides an update on neuroendocrine and immune perturbations associated with PTSD with and without cooccurring MDD to suggest links to health and possible mechanisms underlying the observed sex disparity in the development of PTSD.

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Oral combination of eugenol oleate and miltefosine induce immune response during experimental visceral leishmaniasis through nitric oxide generation with advanced cytokine demand

Cytokine ◽

10.1016/j.cyto.2021.155623 ◽

2021 ◽

Vol 146 ◽

pp. 155623

Author(s):

Amrita Kar ◽

Mamilla R. Charan Raja ◽

Adithyan Jayaraman ◽

Sujatha Srinivasan ◽

Joy Debnath ◽

...

Keyword(s):

Nitric Oxide ◽

Immune Response ◽

Visceral Leishmaniasis

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The Pivotal Role of Signal Regulatory Protein α in Exacerbating Pulmonary Fibrosis Complicated with Bacterial Infection

Journal of Immune Research ◽

10.26420/jimmunres.2021.1039 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yamaguchi R ◽

◽

Sakamoto A ◽

Haraguchi M ◽

Narahara S ◽

...

Keyword(s):

Immune Response ◽

Pulmonary Fibrosis ◽

Bacterial Infection ◽

Signaling Pathway ◽

Regulatory Protein ◽

Interferon Regulatory Factor ◽

Regulatory Factor ◽

Interferon Regulatory Factor 1 ◽

Th1 Immune Response

The pathogenesis of pulmonary fibrosis remains unknown. However, bacterial infections in patients with idiopathic pulmonary fibrosis are a serious complication that exacerbate the disease. Serum levels of Surfactant Protein D (SPD) are known to be elevated in patients with pulmonary fibrosis, but the role of SPD in pulmonary fibrosis complicated with bacterial infection is unknown. Lipopolysaccharide upregulates Interleukin (IL)-12p40 expression and IL-12p40 promotes Interferon Gamma (IFNγ) production to induce the T helper cell 1 (Th1) immune response via Signal Transducers and Activators of Transcription 4 (STAT4) signaling. A lack of IFNγ shifts the immune response from Th1 to Th2. IL-4 is a profibrotic Th2 cytokine that activates fibroblasts. Granulocyte-macrophage colony-stimulating factor induced by IL-1 and TNFα during the Th1 immune response upregulates Signal Regulatory Protein α (SIRPα) expression. Interferon Regulatory Factor 1 (IRF1) functions as the promoter activator of IL-12p40 after stimulation with LPS. SPD is a ligand for SIRPα, and SPD/SIRPα ligation activates the Mitogen-Activated Protein Kinase (MAPK)/Extracellular Signal-Related Kinase (ERK) signal cascade; ERK downregulates Interferon Regulatory Factor 1 (IRF1) expression. Consequently, the SPD/SIRPα signaling pathway decreases IL-12p40 production in human macrophages after exposure to LPS. IL-12p40 is a key immunoregulatory factor in bacterial infection that promotes production of IFNγ by T lymphocytes. Pulmonary fibroblasts are activated by IL-4/IL-4R ligation. IFNγ induces IRF1 via STAT1 signaling, and IRF1 acts as the promoter repressor of IL-4 to attenuate its production. IFNγ also inhibits IL-4R expression. A reduction in IFNγ induced by IL-12p40 deficiency via the SPD/SIRPα signaling pathway enhances IL-4 and IL-4R expression to augment the activity of fibroblasts. This finding indicates that pulmonary fibrosis is exacerbated by SPD/SIRPα signaling during bacterial infection.

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Importance of EMT Factor ZEB1 in cDC1 “MutuDC Line” Mediated Induction of Th1 Immune Response

Frontiers in Immunology ◽

10.3389/fimmu.2018.02604 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 4

Author(s):

Shuchi Smita ◽

Abdul Ahad ◽

Arup Ghosh ◽

Viplov K. Biswas ◽

Marianna M. Koga ◽

...

Keyword(s):

Immune Response ◽

Th1 Immune Response

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Cytokine expression in the duodenal mucosa of patients with visceral leishmaniasis

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86822010000400011 ◽

2010 ◽

Vol 43 (4) ◽

pp. 393-395 ◽

Cited By ~ 4

Author(s):

Kleber Giovanni Luz ◽

Felipe Francisco Tuon ◽

Maria Irma Seixas Duarte ◽

Guilherme Mariz Maia ◽

Paulo Matos ◽

...

Keyword(s):

Immune Response ◽

Gastrointestinal Tract ◽

Visceral Leishmaniasis ◽

Intestinal Bacteria ◽

Duodenal Mucosa ◽

Control Group ◽

Tnf Α ◽

Organ Specific ◽

Ifn Γ

INTRODUCTION: Visceral leishmaniasis (VL) is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL. METHODS: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-γ, TNF-α and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed. RESULTS: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p < 0.05). No differences in the expression of CD8, TNF-α, IL-10 or IL-4 were demonstrated. The number of cells expressing IFN-γ was lower in the VL patients (p < 0.05). CONCLUSIONS: Low levels of cytokines were found in the gastrointestinal tract of patients with VL. This pattern was not found in other organs affected by the disease. Immunotolerance of this tissue against Leishmania could explain these findings, as occurs with intestinal bacteria.

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