scholarly journals Development of Cutaneous Leishmaniasis after Leishmania Skin Test

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Paulo R. Machado ◽  
Augusto M. Carvalho ◽  
Gustavo U. Machado ◽  
Marina L. Dantas ◽  
Sérgio Arruda
Keyword(s):  
Immune Response ◽  
Cutaneous Leishmaniasis ◽  
Skin Test ◽  
Mononuclear Cells ◽  
Previous History ◽  
Self Healing ◽  
Necrosis Factor Alpha ◽  
Cutaneous Ulcer ◽  
The Right

Thirty-year-old female with a previous history of a cutaneous ulcer suspicious of leishmaniasis 20 years ago presented with a new complaint of a depressed papular lesion8×7 mm in the right lower extremity. The lesion was of 10-day duration. Because early cutaneous leishmaniasis (CL) lesions may have a non-ulcerated appearance, a Leishmania skin test (LST) was performed on the forearm with a strong positive result (38×32 mm). After 8 days, the lesion in the leg, which was diagnosed as folliculitis, completely healed. However, a typical CL ulcer (26×24 mm) developed at the LST site. Histopathology of the new lesion did not identifiy parasites, but the findings were consistent with a diagnosis of CL. Further analysis identified amastigotes by immunohistochemical stain. Mononuclear cells harvested from the patient were stimulated with Leishmania antigen and showed high levels of production of both tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ): 2,943 pg/mL and 2,313 pg/mL, respectively. After 40 days of treatment with antimony and pentoxifylline, the ulcer resolved. The development of CL at the LST site suggests a strong Th1 immune response, and it is anin vivodocumentation of the role of the host immune response in the pathology of CL. It teaches us that LST should be cautiously, if at all, used in patients with self-healing CL ulcers.

scholarly journals A 70-Kilodalton Recombinant Heat Shock Protein ofCandida albicans Is Highly Immunogenic and Enhances Systemic Murine Candidiasis

1998 ◽  
Vol 66 (5) ◽  
pp. 2154-2162 ◽  
Author(s):  
Carla Bromuro ◽  
Roberto La Valle ◽  
Silvia Sandini ◽  
Francesca Urbani ◽  
Clara M. Ausiello ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Mononuclear Cells ◽  
Cell Mediated Immunity ◽  
Healthy Human ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Ifn Γ

ABSTRACT The 70-kDa recombinant Candida albicans heat shock protein (CaHsp70) and its 21-kDa C-terminal and 28-kDa N-terminal fragments (CaHsp70-Cter and CaHsp70-Nter, respectively) were studied for their immunogenicity, including proinflammatory cytokine induction in vitro and in vivo, and protection in a murine model of hematogenous candidiasis. The whole protein and its two fragments were strong inducers of both antibody (Ab; immunoglobulin G1 [IgG1] and IgG2b were the prevalent isotypes) and cell-mediated immunity (CMI) responses in mice. CaHsp70 preparations were also recognized as CMI targets by peripheral blood mononuclear cells of healthy human subjects. Inoculation of CaHsp70 preparations into immunized mice induced rapid production of interleukin-6 (IL-6) and tumor necrosis factor alpha, peaking at 2 to 5 h and declining within 24 h. CaHsp70 and CaHsp70-Cter also induced gamma interferon (IFN-γ), IL-12, and IL-10 but not IL-4 production by CD4+ lymphocytes cocultured with splenic accessory cells from nonimmunized mice. In particular, the production of IFN-γ was equal if not superior to that induced in the same cells by whole, heat-inactivated fungal cells or the mitogenic lectin concanavalin A. In immunized mice, however, IL-4 but not IL-12 was produced in addition to IFN-γ upon in vitro stimulation of CD4+ cells with CaHsp70 and CaHsp70-Cter. These animals showed a decreased median survival time compared to nonimmunized mice, and their mortality was strictly associated with organ invasion by fungal hyphae. Their enhanced susceptibility was attributable to the immunization state, as it did not occur in congenitally athymic nude mice, which were unable to raise either Ab or CMI responses to CaHsp70 preparations. Together, our data demonstrate the elevated immunogenicity of CaHsp70, with which, however, no protection against but rather some enhancement of Candida infection seemed to occur in the mouse model used.

Establishment of a murine model of cerebral malaria in KunMing mice infected with Plasmodium berghei ANKA

Parasitology ◽  
2016 ◽  
Vol 143 (12) ◽  
pp. 1672-1680 ◽  
Author(s):  
YAN DING ◽  
WENYUE XU ◽  
TAOLI ZHOU ◽  
TAIPING LIU ◽  
HONG ZHENG ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Cerebral Malaria ◽  
Plasmodium Berghei ◽  
Blood Cells ◽  
Mononuclear Cells ◽  
Clinical Signs ◽  
Necrosis Factor Alpha ◽  
Experimental Cerebral Malaria ◽  
Km Mice

SUMMARYMalaria remains one of the most devastating diseases. Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection resulting in high mortality and morbidity worldwide. Analysis of precise mechanisms of CM in humans is difficult for ethical reasons and animal models of CM have been employed to study malaria pathogenesis. Here, we describe a new experimental cerebral malaria (ECM) model with Plasmodium berghei ANKA infection in KunMing (KM) mice. KM mice developed ECM after blood-stage or sporozoites infection, and the development of ECM in KM mice has a dose-dependent relationship with sporozoites inoculums. Histopathological findings revealed important features associated with ECM, including accumulation of mononuclear cells and red blood cells in brain microvascular, and brain parenchymal haemorrhages. Blood–brain barrier (BBB) examination showed that BBB disruption was present in infected KM mice when displaying clinical signs of CM. In vivo bioluminescent imaging experiment indicated that parasitized red blood cells accumulated in most vital organs including heart, lung, spleen, kidney, liver and brain. The levels of inflammatory cytokines interferon-gamma, tumour necrosis factor-alpha, interleukin (IL)-17, IL-12, IL-6 and IL-10 were all remarkably increased in KM mice infected with P. berghei ANKA. This study indicates that P. berghei ANKA infection in KM mice can be used as ECM model to extend further research on genetic, pharmacological and vaccine studies of CM.

C5a Depletion As a Novel Strategy to Inhibit T Regulatory Cells and Enhance Antigen-Specific Immune Responses

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3285-3285
Author(s):  
Suresh Veeramani ◽  
George J. Weiner
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Regulatory Cells ◽  
Complement Components ◽  
Novel Strategy

Abstract Abstract 3285 Background: The complement system has complex activity that impacts on the immune response in a broad variety of ways. The current study was designed to assess the effect of complement components, specifically C5a, on the immune regulatory cells and on the development of an antigen-specific active immune response. Methods: Myeloid dendritic cells (mDCs), enriched from healthy human peripheral blood mononuclear cells, were pulsed with antigen (tetanus toxoid) and co-cultured with autologous, enriched human CD4+ T cells in the presence of various purified complement components. The percent of CD4+ T-cells that were CD25highFoxp3+ (henceforth referred to as Tregs) was determined. The presence of cytokines in supernatant of mDCs cultured with purified complement proteins was also evaluated. In murine models, the effect of C5a on in vivo induction of Tregs and on the development of immune response to ovalbumin was determined by analyzing anti-ovalbumin antibody. This was done in C5-sufficient (B10-D2-HC1) and C5-deficient (B10-D2-HC0) mice immunized with 100 μg of ovalbumin, and in wild type C57Bl/6 mice immunized with 100 μg of ovalbumin along with either irrelevant rat IgG2a (Ova+Isotype control) or rat anti-mouse C5a antibody (Ova+anti-C5a Ab). Results: In Vitro: In Vivo: Conclusions: Presence of C5a in the immune microenvironment results in increased generation of Treg cells and leads to dampening of antigen-specific immune responses. Absence or depletion of C5a results in a drop in the Tregs and a higher antigen-specific immune response. Ongoing studies are exploring the use of C5a depletion as a novel strategy to overcome the low immunogenicity of vaccines, such as cancer vaccines. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Carbohydrate Lectin Receptor Dectin-1 Mediates the Immune Response to Exserohilum rostratum

2016 ◽  
Vol 85 (3) ◽  
Author(s):  
Jennifer L. Reedy ◽  
Paige E. Negoro ◽  
Marianela Feliu ◽  
Allison K. Lord ◽  
Nida S. Khan ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cell ◽  
Wide Spectrum ◽  
Granulomatous Inflammation ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Macrophage Response ◽  
Lectin Receptor ◽  
Exserohilum Rostratum

ABSTRACT Dematiaceous molds are found ubiquitously in the environment and cause a wide spectrum of human disease, including infections associated with high rates of mortality. Despite this, the mechanism of the innate immune response has been less well studied, although it is key in the clearance of fungal pathogens. Here, we focus on Exserohilum rostratum, a dematiaceous mold that caused 753 infections during a multistate outbreak due to injection of contaminated methylprednisolone. We show that macrophages are incapable of phagocytosing Exserohilum. Despite a lack of phagocytosis, macrophage production of tumor necrosis factor alpha is triggered by hyphae but not spores and depends upon Dectin-1, a C-type lectin receptor. Dectin-1 is specifically recruited to the macrophage-hyphal interface but not the macrophage-spore interface due to differences in carbohydrate antigen expression between these two fungal forms. Corticosteroid and antifungal therapy perturb this response, resulting in decreased cytokine production. In vivo soft tissue infection in wild-type mice demonstrated that Exserohilum provokes robust neutrophilic and granulomatous inflammation capable of thwarting fungal growth. However, coadministration of methylprednisolone acetate results in robust hyphal tissue invasion and a significant reduction in immune cell recruitment. Our results suggest that Dectin-1 is crucial for macrophage recognition and the macrophage response to Exserohilum and that corticosteroids potently attenuate the immune response to this pathogen.

scholarly journals Optimizing a Protocol to Assess Immune Responses after SARS-CoV-2 Vaccination in Kidney-Transplanted Patients: In Vivo DTH Cutaneous Test as the Initial Screening Method

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1315
Author(s):  
Yvelise Barrios ◽  
Aurelio Rodriguez ◽  
Andrés Franco ◽  
Cristina Alava-Cruz ◽  
Domingo Marrero-Miranda ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Skin Test ◽  
Natural Infection ◽  
Screening Method ◽  
Delayed Type Hypersensitivity ◽  
Interferon Gamma Release Assay ◽  
Cutaneous Test

Previously, the delayed-type hypersensitivity (DTH) cutaneous test with the spike protein of SARS-CoV-2 has been shown to be a simple in vivo method to measure T-cell functionality after natural infection and in vaccinated individuals. Methods: Twenty-five kidney-transplanted recipients were immunized with two doses of the mRNA-based Pfizer–BioNTech COVID19 vaccine three weeks apart. Cell-immune response (CIR) was evaluated ten weeks later using an in vivo DTH skin test and in vitro with an interferon gamma release assay (IGRA). Humoral Immune Response (HIR) was determined by the measurement of specific IgG anti-S1 SARS-CoV-2. Results: Ten weeks after the second dose of the vaccine, 23 out of 25 transplanted patients had a positive DTH skin test, while in vitro CIR was considered positive in 20 patients. Unspecific stimulation was positive in all 25 patients, showing no T-cell defect. Seven out of twenty-five patients had a negative specific anti-spike IgG. CIR was positive in all immune-competent control patients. Conclusions: DTH is a useful, simple, and cheaper tool that can be used to assess cellular immune response, with an excellent correlation with the in vitro CIR. CIR assessment after vaccination in these immunocompromised patients is an excellent complement to HIR-based methods. This skin test could be used if classical in vitro methods cannot be applied.

scholarly journals Histological observations on Montenegro's reaction in man

1989 ◽  
Vol 31 (4) ◽  
pp. 256-261 ◽  
Author(s):  
Wilson Mayrink ◽  
Antonio Pedro M. Schettini ◽  
Paul Williams ◽  
Pedro Raso ◽  
Paulo Araujo Magalhães ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Skin Test ◽  
Diagnostic Method ◽  
Previous History ◽  
Histological Changes ◽  
Histological Studies ◽  
Vaccine Trials ◽  
American Cutaneous Leishmaniasis ◽  
History Of

The Montenegro skin test is widely used as a diagnostic method for American cutaneous leishmaniasis (ACL) but little is known about the histological changes that occur in the skin after administration of the antigen. This report is based on histological studies of biopsied material obtained, from inoculation sites, 48 hours after individuals had been given intradermal injections with a standardized Montenegro antigen. The material examined was obtained from four distinctly different test groups: naturally infected patients with parasitologically proved ACL and with positive Montenegro's reaction; individuals without previous history of ACL and not previously tested with Montenegro antigen; participants in anti-ACL vaccine trials who developed positive reactions to Montenegro antigen after vaccination; other participants in vaccine trials who had negative Montenegro responses after vaccination or had served as controls in the trials. The histological pictures of each group are described and discussed. Histologically, the reactions of vaccinated individuals were indistinguishable from those with naturally acquired infections.

scholarly journals Interdigital skin test for evaluation of delayed hypersensitivity and monitoring cell-mediated immune responses in chickens

2007 ◽  
Vol 23 (5-6-2) ◽  
pp. 223-228 ◽  
Author(s):  
B. Miljkovic ◽  
L. Peric ◽  
M. Velhner
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Skin Test ◽  
Skin Testing ◽  
Intradermal Injection ◽  
Delayed Hypersensitivity ◽  
Skin Thickness ◽  
Strong Immune Response ◽  
Cell Mediated Immune Response

A skin test to assess cell mediated delayed hypersensitivity (DH) used to evaluated immune response of chickens. Results of many study indicated, that skin testing is especially useful as a simple in vivo screening to evaluate normal and suppressed T-cell mediated DH. Chickens were sensitized with using mitogens, B and T-cell dependent antigen by intradermal injection. The most feathered skin of chickens is too thin for adequate intradermal injections, so the wattle is the standard site for skin testing, however, in younger than 2 or 3 weeks old chickens, the wattle is undeveloped and intradermal injection and measurement of response are difficult. A simple interdigital skin used by many of the authors. Skin swelling response and DH reaction were measured in mm before injections and after. The skin test and DH in vivo results edemas-initiating characteristics of sensitizing agents, which increase in skin thickness detectable after 4- 6 hours of application. Many of investigation results suggests that healthy chickens are able to have strong immune response and support the concept that some changes in the cell-mediated immune response and other pathogens may potentially affect immune response.

scholarly journals Spermine Inhibits Proinflammatory Cytokine Synthesis in Human Mononuclear Cells: A Counterregulatory Mechanism that Restrains the Immune Response

1997 ◽  
Vol 185 (10) ◽  
pp. 1759-1768 ◽  
Author(s):  
Minghuang Zhang ◽  
Theresa Caragine ◽  
Haichao Wang ◽  
Pamela S. Cohen ◽  
Galina Botchkina ◽  
...  
Keyword(s):  
Immune Response ◽  
Proinflammatory Cytokines ◽  
Proinflammatory Cytokine ◽  
Mononuclear Cells ◽  
Molecular Mimicry ◽  
Human Peripheral Blood ◽  
Interleukin 1 ◽  
Peripheral Blood Mononuclear ◽  
Cytokine Synthesis

The local production of proinflammatory cytokines mediates the host response to inflammation, infection, and injury, whereas an overexpression of these mediators can injure or kill the host. Recently, we identified a class of multivalent guanylhydrazone compounds that are effective inhibitors of proinflammatory cytokine synthesis in monocytes/macrophages. The structure of one such cationic molecule suggested a molecular mimicry with spermine, a ubiquitous endogenous biogenic amine that increases significantly at sites of inflammation and infection. Here, we addressed the hypothesis that spermine might counterregulate the innate immune response by downregulating the synthesis of potentially injurious cytokines. When spermine was added to cultures of human peripheral blood mononuclear cells stimulated with lipopolysaccharide (LPS), it effectively inhibited the synthesis of the proinflammatory cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-6, MIP-1α, and MIP-1β. The inhibition of cytokine synthesis was specific and reversible, with significant inhibition of TNF synthesis occurring even when spermine was added after LPS. The mechanism of spermine-mediated cytokine suppression was posttranscriptional and independent of polyamine oxidase activity. Local administration of spermine in vivo protected mice against the development of acute footpad inflammation induced by carrageenan. These results identify a distinct molecular counterregulatory role for spermine in downregulating the monocyte proinflammatory cytokine response.

scholarly journals Activation of natural regulatory T cells by IgG Fc–derived peptide “Tregitopes”

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3303-3311 ◽  
Author(s):  
Anne S. De Groot ◽  
Leonard Moise ◽  
Julie A. McMurry ◽  
Erik Wambre ◽  
Laurence Van Overtvelt ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Regulatory T Cell ◽  
Mononuclear Cells ◽  
T Cell Epitopes ◽  
Peripheral Blood Mononuclear ◽  
Murine Homologue

Abstract We have identified at least 2 highly promiscuous major histocompatibility complex class II T-cell epitopes in the Fc fragment of IgG that are capable of specifically activating CD4+CD25HiFoxP3+ natural regulatory T cells (nTRegs). Coincubation of these regulatory T-cell epitopes or “Tregitopes” and antigens with peripheral blood mononuclear cells led to a suppression of effector cytokine secretion, reduced proliferation of effector T cells, and caused an increase in cell surface markers associated with TRegs such as FoxP3. In vivo administration of the murine homologue of the Fc region Tregitope resulted in suppression of immune response to a known immunogen. These data suggest that one mechanism for the immunosuppressive activity of IgG, such as with IVIG, may be related to the activity of regulatory T cells. In this model, regulatory T-cell epitopes in IgG activate a subset of nTRegs that tips the resulting immune response toward tolerance rather than immunogenicity.

scholarly journals IL-18 mediates sickle cell cardiomyopathy and ventricular arrhythmias

Blood ◽  
2020 ◽  
Author(s):  
Akash Gupta ◽  
Yu-Dong Fei ◽  
Tae Yun Kim ◽  
An Xie ◽  
Ken Batai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sickle Cell ◽  
Cardiac Fibrosis ◽  
Mononuclear Cells ◽  
Humanized Mouse Model ◽  
Peripheral Blood Mononuclear ◽  
Patients At Risk ◽  
The Right ◽  
Il18 Gene

Previous reports indicate IL18 is a novel candidate gene for diastolic dysfunction in sickle cell disease (SCD)-related cardiomyopathy. We hypothesize that IL-18 mediates the development of cardiomyopathy and ventricular tachycardia (VT) in SCD. Compared to control (CTR) mice, a "humanized" mouse model of SCD exhibited increased cardiac fibrosis, prolonged action potential duration (APD), higher VT inducibility in vivo, higher cardiac NFκB phosphorylation and circulating IL-18 levels, as well as reduced voltage-gated potassium channel expression, translating to reduced outward potassium current (Ito) in isolated cardiomyocytes. IL-18 administration to isolated mice hearts resulted in VTs, originating from the right ventricle, and further reduced Ito in SCD mice cardiomyocytes. Sustained IL-18 inhibition via IL-18 binding protein resulted in decreased cardiac fibrosis and NFκB phosphorylation, improved diastolic function, normalized electrical remodeling and attenuated IL-18-mediated VT in SCD mice. Patients with SCD and either myocardial fibrosis or increased QTc displayed greater IL18 gene expression in peripheral blood mononuclear cells (PBMC), with QTc strongly correlated with plasma IL-18 levels. PBMC-derived IL18 gene expression was increased in non-surviving over surviving subjects. IL-18 is a mediator of sickle cell cardiomyopathy and VT in mice and a novel therapeutic target in patients at risk for sudden death.

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