Aspergillosis In Mice Research Articles

Therapeutic potential of Calotropis gigantea extract against invasive pulmonary aspergillosis

Objective: To characterize the antifungal activity of methanolic leaf extract of Calotropis gigantea alone or in combination with amphotericin B against invasive pulmonary aspergillosis in mice. Methods: GC/MS was used for analysis of active constituents of Calotropis gigantea extract. Spore germination assay and broth micro-dilution method were used to determine antifungal potential of Calotropis gigantea/amphotericin B against Aspergillus fumigatus. Neutropenic mice were randomly assigned into 5 groups: group 1 was neutropenic (control); group 2 was infected with Aspergillus fumigatus; group 3 was infected with Aspergillus fumigatus, and treated with Calotropis gigantea extract; group 4 was infected with Aspergillus fumigatus and treated with amphotericin B; group 5 was infected with Aspergillus fumigatus and treated with both Calotropis gigantea extract and amphotericin B. Fresh lung tissues were histopathologically examined. Fungal burden and gliotoxin concentration were evaluated in lung tissues. Catalase, superoxide dismutase, and malondialdehyde content were determined in lung tissues. Myeloperoxidase, tumor necrosis factor-alpha, interleukin-1, and interleukin-17 were also estimated by the sandwich enzyme-linked immuno-sorbent assay. Results: Calotropis gigantea/amphotericin B had a minimum inhibitory concentration and minimum fungicidal concentration of 80 and 160 μg/mL, respectively, for Aspergillus fumigatus. Additionally, Calotropis gigantea/amphotericin B significantly reduced lung fungal burden by 72.95% and inhibited production of gliotoxin in lung tissues from 6 320 to 1 350 μg/g lung. Calotropis gigantea/amphotericin B reduced the oxidative stress of the lung via elevating the activity of antioxidant enzymes and decreasing the levels of lipid peroxidation. Myeloperoxidase activity and the production of pro-inflammatory cytokines were also significantly reduced. Scanning electron microscopy revealed deteriorations in the hyphae ultrastructure in Calotropis gigantea/amphotericin B treated Aspergillus fumigatus and leak of cellular components after damage of the cell wall. In vivo study revealed the suppression of lung tissue damage in mice of invasive pulmonary aspergillosis, which was improved with Calotropis gigantea/amphotericin B compared to the control group. Conclusions: Calotropis gigantea/amphotericin B is a promising treatment to reduce lung fungal burden and to improve the drugs’ therapeutic effect against invasive pulmonary aspergillosis.

Proteome analysis of bronchoalveolar lavage fluids reveals host and fungal proteins highly expressed during invasive pulmonary aspergillosis in mice and humans

ABSTRACT Invasive pulmonary aspergillosis (IPA) is a severe infection that is difficult to diagnose due to the ubiquitous presence of fungal spores, the underlying diseases of risk patients, and limitations of currently available markers. In this study, we performed a comprehensive liquid chromatography tandem mass spectrometry (LC-MS/MS)-based identification of host and fungal proteins expressed during IPA in mice and humans. The proteomic analysis of bronchoalveolar lavage samples of individual IPA and control cases allowed the description of common host factors that had significantly increased abundance in both infected animals and IPA patients compared to their controls. Although increased levels of these individual host proteins might not be sufficient to distinguish bacterial from fungal infection, a combination of these markers might be beneficial to improve diagnosis. We also identified 16 fungal proteins that were specifically detected during infection and may be valuable candidates for biomarker evaluation.

Diphenyl diselenide and its interaction with antifungals against Aspergillus spp.

The activity of diphenyl diselenide (PhSe)2 alone and in combination with itraconazole, voriconazole, and caspofungin, is described against three of the most pathogenic Aspergillus sections. (PhSe)2 may prove useful in therapy of infection in future; further study is required.

Tissue Distribution and Penetration of Isavuconazole at the Site of Infection in Experimental Invasive Aspergillosis in Mice with Underlying Chronic Granulomatous Disease.

Isavuconazole, the active moiety of the prodrug isavuconazonium sulfate, has potent activity against a wide spectrum of fungal pathogens and is approved for the treatment of invasive aspergillosis, yet little is known about the tissue penetration of isavuconazole at the target sites of infection. Here, we explored the spatial and quantitative distribution of isavuconazole in tissue lesions in experimental pulmonary aspergillosis established in mice with chronic granulomatous disease (CGD) (gp91phox-). Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and laser capture microdissection (LCM)-directed high-pressure liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) were used to analyze infected lungs and brain tissues collected 1, 3, 6, and 24 h after a single oral administration of the prodrug at a dose of 256 mg/kg of body weight (corresponding to 122.9 mg/kg of isavuconazole). Drug enrichment within granulomatous lesions was observed in lung tissue at 1 h postdose, although drug levels quickly equilibrated afterwards between lesion and nonlesion areas. A prominent antifungal effect in the infected lung tissue was revealed by histopathological analysis. Isavuconazole also penetrated into the brain with high efficiency. These data further support the value of isavuconazole to treat patients with invasive aspergillosis.

A novel monoclonal antibody against enolase antigen of Aspergillus fumigatus protects experimental aspergillosis in mice.

Aspergillus fumigatus is one of the most common opportunistic fungal pathogens responsible for a variety of diseases in human, from allergic bronchopulmonary aspergillosis to chronic pulmonary aspergillosis, mostly in immunocompromized patients. In this study, one monoclonal antibody MAb R-5 (IgM) raised against enolase cell surface protein of A. fumigatus exhibited significant inhibition of spore germination in A. fumigatus (88.3%), Aspergillus flavus (57.4%) and Aspergillus niger (30.6%). The MAb R-5 also showed in vitro fungicidal activity against these species as follows: A. fumigatus (24.1%), A. flavus (13.3%) and A. niger (8.8%). These findings were supported by the indirect immunofluorescence microscopy, where the antibody showed binding with germinated spores and hyphae of A. fumigatus as well as A. flavus and A. niger.In vivo protective effect of MAb R-5 was evaluated in BALB/c mice challenged intravenously with A. fumigatus spores, where a significant reduction in CFU (85.9%) was observed in kidney tissue. The mean survival time of mice treated with MAb R-5 (18.5 days) was also enhanced compared to control (6.5 days). These results indicate that MAb R-5 could be valuable in diagnosis as well as in the treatment of broad range of Aspergillus infections.

Host immune status-specific production of gliotoxin and bis-methyl-gliotoxin during invasive aspergillosis in mice

Delayed diagnosis in invasive aspergillosis (IA) contributes to its high mortality. Gliotoxin (GT) and bis-methyl-gliotoxin (bmGT) are secondary metabolites produced by Aspergillus during invasive, hyphal growth and may prove diagnostically useful. Because IA pathophysiology and GT’s role in virulence vary depending on the underlying host immune status, we hypothesized that GT and bmGT production in vivo may differ in three mouse models of IA that mimic human disease. We defined temporal kinetics of GT and bmGT in serum, bronchoalveolar lavage fluid (BALF) and lungs of A. fumigatus-infected chronic granulomatous disease (CGD), hydrocortisone-treated, and neutropenic mice. We harvested lungs for assessment of fungal burden, histology and GT/bmGT biosynthetic genes’ mRNA induction. GT levels were higher in neutropenic versus CGD or steroid-treated lungs. bmGT was persistently detected only in CGD lungs. GT, but not bmGT, was detected in 71% of sera and 50% of BALF of neutropenic mice; neither was detected in serum/BALF of CGD or steroid-treated mice. Enrichment of GT in Aspergillus-infected neutropenic lung correlated with fungal burden and hyphal length but not induction of GT biosynthetic genes. In summary, GT is detectable in mouse lungs, serum and BALF during neutropenic IA, suggesting that GT may be useful to diagnose IA in neutropenic patients.

Longitudinal, in vivo assessment of invasive pulmonary aspergillosis in mice by computed tomography and magnetic resonance imaging

Invasive aspergillosis is an emerging threat to public health due to the increasing use of immune suppressive drugs and the emergence of resistance against antifungal drugs. To deal with this threat, research on experimental disease models provides insight into the pathogenesis of infections caused by susceptible and resistant Aspergillus strains and by assessing their response to antifungal drugs. However, standard techniques used to evaluate infection in a preclinical setting are severely limited by their invasive character, thereby precluding evaluation of disease extent and therapy effects in the same animal. To enable non-invasive, longitudinal monitoring of invasive pulmonary aspergillosis in mice, we optimized computed tomography (CT) and magnetic resonance imaging (MRI) techniques for daily follow-up of neutropenic BALB/c mice intranasally infected with A. fumigatus spores. Based on the images, lung parameters (signal intensity, lung tissue volume and total lung volume) were quantified to obtain objective information on disease onset, progression and extent for each animal individually. Fungal lung lesions present in infected animals were successfully visualized and quantified by both CT and MRI. By using an advanced MR pulse sequence with ultrashort echo times, pathological changes within the infected lung became visually and quantitatively detectable at earlier disease stages, thereby providing valuable information on disease onset and progression with high sensitivity. In conclusion, these non-invasive imaging techniques prove to be valuable tools for the longitudinal evaluation of dynamic disease-related changes and differences in disease severity in individual animals that might be readily applied for rapid and cost-efficient drug screening in preclinical models in vivo.

Application of a low molecular weight antifungal protein from Penicillium chrysogenum (PAF) to treat pulmonary aspergillosis in mice

PAF, a small antifungal protein from Penicillium chrysogenum, inhibits the growth of several pathogenic filamentous fungi, including members of the Aspergillus genus. PAF has been proven to have no toxic effects in vivo in mice by intranasal application. To test its efficacy against invasive pulmonary aspergillosis (IPA), experiments were carried out in mice suffering from IPA. Adult mice were immunosuppressed and then infected with Aspergillus fumigatus. After stable infection, the animals were inoculated with PAF intranasally at a concentration of 2.7 mg/kg twice per day. At this concentration—which is highly toxic in vitro to A. fumigatus—the mortality of the animals was slightly delayed but finally all animals died. Histological examinations revealed massive fungal infections in the lungs of both PAF-treated and untreated animal groups. Because intranasally administered PAF was unable to overcome IPA, modified and combined therapies were introduced. The intraperitoneal application of PAF in animals with IPA prolonged the survival of the animals only 1 day. Similar results were obtained with amphotericin B (AMB), with PAF and AMB being equally effective. Combined therapy with AMB and PAF—which are synergistic in vitro—was found to be more effective than either AMB or PAF treatment alone. As no toxic effects of PAF in mammals have been described thus far, and, moreover, there are so far no A. fumigatus strains with reported inherent or acquired PAF resistance, it is worth carrying out further studies to introduce PAF as a potential antifungal drug in human therapy.Emerging Microbes & Infections (2016) 5, e114; doi:10.1038/emi.2016.116; published online 9 November 2016

Whole glucan particles as a vaccine against systemic coccidioidomycosis.

We reported previously that yeast-derived whole glucan particles (WGPs), with or without conjugation to BSA, used as a vaccine protected against systemic aspergillosis in mice. Here, we examined their utility as a potential vaccine against coccidioidomycosis. WGPs were prepared from Saccharomyces cerevisiae; conjugation with BSA (WGP-BSA) was done using 1-cyano-4-dimethylaminopyridinium tetrafluoroborate-mediated conjugation. Heat-killed S. cerevisiae (HKY) was used as a positive-control vaccine. CD-1 mice were vaccinated with WGPs or WGP-BSA, HKY or PBS once weekly, beginning 21 days prior to infection. Mice were infected intravenously with arthroconidia of Coccidioides posadasii. In the low-mortality study, 50 % of PBS-treated controls died. Only WGP-BSA at 0.6 mg per dose induced significant protection compared with PBS treatment. All surviving mice were infected in all three organs examined. Those given WGP-BSA at 0.6 mg per dose had fewer c.f.u. in liver and lungs (P = 0.04), and those given WGPs at 6 mg per dose had fewer in lungs (P < 0.02), compared with PBS. In the high-mortality study, 90 % of PBS mice died. Vaccination with HKY, and WGPs or WGP-BSA at 6 or 12 mg per dose significantly prolonged survival (P ≤ 0.05). No surviving mice were free of infection. HKY and WGP-BSA at 12 mg per dose reduced c.f.u. in the liver and lungs (P < 0.05) and WGP-BSA at 6 mg per dose reduced c.f.u. in the lungs (P < 0.05); unconjugated WGPs did not reduce infection. WGPs or WGP-BSA acted as a vaccine that protected against mortality caused by coccidioidomycosis. Thus, WGP protection against coccidioidomycosis and aspergillosis provides the basis for development of a pan-fungal vaccine.

Aspergillus flavus induces granulomatous cerebral aspergillosis in mice with display of distinct cytokine profile

Aspergillus flavus is one of the leading Aspergillus spp. resulting in invasive aspergillosis of central nervous system (CNS) in human beings. Immunological status in aspergillosis of central nervous system remains elusive in case of both immunocompetent and immunocompromised patients. Since cytokines are the major mediators of host response, evaluation of disease pathology along with cytokine profile in brain may provide snapshots of neuro-immunological response. An intravenous model of A. flavus infection was utilized to determine the pathogenicity of infection and cytokine profile in the brain of male BALB/c mice. Enumeration of colony forming units and histopathological analyses were performed on the brain tissue at distinct time periods. The kinetics of cytokines (TNF-α, IFN-γ, IL-12/IL-23p40, IL-6, IL-23, IL-17A and IL-4) was evaluated at 6, 12, 24, 48, 72 and 96h post infection (hPI) in brain homogenates using murine cytokine specific enzyme linked immunosorbent assay. Histological analysis exhibited the hyphae with leukocyte infiltrations leading to formation of granulomata along with ischemia and pyknosis of neurons in the brain of infected mice. Diseased mice displayed increased secretion of IFN-γ, IL-12p40 and IL-6 with a concomitant reduction in the secretion of Th2 cytokine IL-4, and Th17 promoting cytokine, IL-23 during the late phase of infection. A.flavus induced inflammatory granulomatous cerebral aspergillosis in mice, characterized by a marked increase in the Th1 cytokines and neurons undergoing necrosis. A marked increase in necrosis of neurons with concurrent inflammatory responses might have led to the host mortality during late phase of infection.

IL-37 inhibits inflammasome activation and disease severity in murine aspergillosis.

Since IL-37 transgenic mice possesses broad anti-inflammatory properties, we assessed whether recombinant IL-37 affects inflammation in a murine model of invasive pulmonary aspergillosis. Recombinant human IL-37 was injected intraperitoneally into mice prior to infection and the effects on lung inflammation and inflammasome activation were evaluated. IL-37 markedly reduced NLRP3-dependent neutrophil recruitment and steady state mRNA levels of IL-1β production and mitigated lung inflammation and damage in a relevant clinical model, namely aspergillosis in mice with cystic fibrosis. The anti-inflammatory activity of IL-37 requires the IL-1 family decoy receptor TIR-8/SIGIRR. Thus, by preventing activation of the NLRP3 inflammasome and reducing IL-1β secretion, IL-37 functions as a broad spectrum inhibitor of the innate response to infection-mediated inflammation, and could be considered to be therapeutic in reducing the pulmonary damage due to non-resolving Aspergillus infection and disease.

Erythropoietin Combined with Liposomal Amphotericin B Improves Outcome during Disseminated Aspergillosis in Mice.

Disseminated aspergillosis is responsible for a high mortality rate, despite the use of antifungal drugs. Adjuvant therapies are urgently needed to improve the outcome. The aim of this study was to demonstrate that the cytoprotective effect of erythropoietin (EPO) combined with amphotericin B can reduce the mortality rate in a murine model of disseminated aspergillosis. After infection with Aspergillus fumigatus, neutropenic mice were randomized to receive vehicle or 7.5 mg/kg liposomal amphotericin B (LAmB) or 7.5 mg/kg LAmB combined with 1000 IU/kg EPO (16 mice per group). Aspergillus galactomannan and organ cultures were performed to evaluate fungal burden at day 5. Cumulative long-term survival was analyzed at day 12 post-infection according to the Kaplan–Meier method. At day 5, fungal burden was similar between non-treated and treated groups. At day 12, mortality rates were 75, 62.5, and 31% in control group, LAmB group, and EPO/LAmB group, respectively. We observed a significant decrease in mortality using EPO/LAmB combination compared to control group (p < 0.01). LAmB single treatment did not improve the survival rate compared to control group (p = 0.155). Our results provide the first evidence that EPO improved the outcome of mice presenting with disseminated aspergillosis when combined with amphotericin B.

Axl receptor blockade protects from invasive pulmonary aspergillosis in mice.

Aspergillus fumigatus is a sporulating fungus found ubiquitously in the environment, which is quickly contained in the immunocompetent host but can cause lethal invasive aspergillosis in the immunocompromised host. We have recently demonstrated that Axl (one member of the Tyro3, Axl, Mertk receptor family) is a key regulator of antiviral immune responses in the lung. In this study, we investigated the role of Axl in antifungal immunity in a model of invasive pulmonary aspergillosis (IPA). In this model, Aspergillus fumigatus conidia were administered into the lungs of neutrophil-depleted mice, and the mice were monitored for survival, lung inflammatory response, and fungal clearance. The lethal effect of IPA was significantly reduced in anti-Axl mAb-treated mice compared with IgG control-treated mice. Targeting Axl significantly inhibited pulmonary inflammation, including the expression of IL-1β, IL-6, TNF-α, and chitinase-like proteins in whole lung. Further, anti-Axl mAb treatment significantly increased M1 macrophages that highly expressed inducible NO synthase and decreased M2 macrophages that expressed Arginase 1 and were found in inflammatory zone protein (Fizz1). More importantly, anti-Axl mAb treatment significantly increased the number of IFN-γ-producing T cells and NK cells compared with the IgG control group during IPA. Together, our results demonstrate that the Axl mAb treatment is protective during invasive aspergillosis in neutropenic mice. Collectively, these data suggest a potential deleterious role for Axl during primary immune responses directed against A. fumigatus and novel therapeutic strategy for IPA.

Therapeutic effect of Sepia ink extract against invasive pulmonary aspergillosis in mice

Invasive pulmonary aspergillosis (IPA) is a life-threatening disease in immunocompromised patients that requires aggressive therapy. Because of the widespread use of antibiotics, corticosteroids, antitumor drugs, and immunosuppressive drugs, the morbidity of IPA is currently increasing. The ink secretion of molluscan species was identified as one of the novel sources of bioactive compounds. So the present study designed to investigate the antifungal and antioxidant effects of Sepia officinalis ink extract against IPA in mice. Eighty neutropenic infected mice were randomly assigned into four main groups (20 mice/group). The 1st group was treated with saline, neutropenic infected, the 2nd group was treated with ink (200mg/kg) and the 3rd group was treated with amphotericin B (150mg/kg) and the 4th group was treated with ink plus amphotericin B (Ink 200mg/kg and AMB 150mg/kg). Treatment was started at 24h after fungal inoculation and was administered for 3 consecutive days. The present study demonstrated good in vitro and in vivo antifungal activity of IE against Aspergillus fumigatus. Compared with IPA group; IE-treated, AMB-treated, and AMB+IE-treated animals had a 67.80%, 83.41%, and 72.68% reduction in the pulmonary fungal burden, respectively. Treatment with IE and/or AMB for one and three days significantly decreased MDA and increased GSH and SOD levels in the lung tissues as compared with the infected untreated group. In conclusion, the results of our in vivo and in vitro studies demonstrate that IE has therapeutic effect against invasive pulmonary aspergillosis via reducing oxidative stress.

Study of immunological aspects of aspergillosis in mice and effect of polyene macrolide antibiotic (SJA-95) and IFN-γ: A possible role of IFN-γ as an adjunct in antifungal therapy

New polyene macrolide antibiotic SJA-95 in free as well as liposomal (lip.) forms, with and without interferon-γ (IFN-γ) was studied in mice model of aspergillosis using biological and biochemical parameters viz. colony forming units (CFU) in liver, spleen, kidney, lung and brain, and serum IgG, and interleukin-4 (IL-4). Treatment with free and lip SJA-95 along with IFN-γ prolonged the survival time, reduced CFU in vital organs, decreased serum IgG and IL-4 levels. SJA-95 lip form showed greater antifungal activity as compared to free form. The combined treatment of lip SJA-95 with IFN-γ showed further enhancement in antifungal activity of SJA-95 (lip). The present experimental findings demonstrated IFN-γ might act as a potent modulator in immune reaction during fungal infection and can be a useful adjunctive in antifungal therapy in the management of deep seated systemic mycoses.

Experimental disseminated aspergillosis in mice: Histopathological study

Objective Systemic response to intravenous administration of Aspergillus fumigatus conidia was investigated in laboratory mice by survival/mortality, peripheral blood leukocyte response and histopathological evaluation of lung, liver, kidney and spleen. Methods Female C57Bl/6 mice were inoculated intravenously with 10 6–5 × 10 7 conidia of A. fumigatus (human isolate). Survival was monitored for two weeks. Histopathological analysis of organ was conducted postmortem and in survivors. Peripheral blood cells and leukocyte aggregation were determined in survivors. Results Administration of all doses of A. fumigatus conidia caused mortality, but the highest mortality rate and the shortest time of survival were noted at the highest doses applied. Increased peripheral blood lymphocyte counts and their propensity to aggregate were observed in survivors. Histological analysis revealed : (1) pulmonary inflammatory response proportional to the applied dose of conidia with detectable fungi in lungs of animals that received the highest applied dose; (2) pronounced kidney inflammatory response with variable intensity of tubular dilation in survivors versus tubular destruction in nonsurvivors and proteinuria as well as hemoglobinuria at the highest doses applied; (3) presence of microabscesses in the liver; (4) white pulp hyperplasia and dose-dependent increase in lymphoid follicles in the spleen of infected animals that survived. Conclusion Lymphocytosis and state of aggregation/adhesion in survivors and local histologically evident inflammatory response in all examined organs of mice characterize the response to systemic application of A. fumigatus conidia. The results obtained may contribute to our understanding of pathological mechanisms underlying disseminated aspergillosis and to the evaluation of therapeutic interventions that might improve survival or lessen pathology.

Experimentally induced invasive aspergillosis in mice

In this study systemic response to intravenous administration of Aspergillus fumigatus conidia was investigated. The intensity of response was evaluated by a survival rate and by histopathological tissue analysis. Administration of all doses (106 - 5x107) of Aspergillus fumigatus conidia caused mortality, but the highest mortality and the shorter time of survival were noted at higher doses applied. At the highest applied dose, the presence of spores and hyphae was noted in lungs and kidneys. Histological analysis revealed the presence of intense inflammatory reaction in lungs, kidneys and spleen. Functional and histological changes observed provide means to study both mechanisms and drug interventions in systemic Aspergillus infection.

Animal models of Aspergillus infection in preclinical trials, diagnostics and pharmacodynamics: What can we learn from them?

Animal models of aspergillosis, particularly those studied in rodents, are an integral part of antifungal drug development. The capacity to control different variables is beneficial, allowing a well defined model system to be used to address various issues of efficacy with monotherapy, combinations, or immunotherapy. One beneficial aspect of the use of animal models is that they enable us to investigate novel indications of drugs prior to a clinical trial or where a clinical trial is impractical. Included in these types of studies is the testing of potentially preventative vaccines. Animal models also are useful for studying diagnostic assays, as well as pharmacology and toxicity. Thus, because of the ability of the best models to mimic human diseases, and our ability to infect genetically identical cohorts of the same age, sex, co-morbidities and risk factors, with an identical challenge inoculum at the same time, we are able to address issues in vivo that cannot be answered by in vitro tests. We also can have sufficient numbers of subjects for statistical analyses, can vary the severity of infection at will and can choose to terminate the experiments to enable using survival or clearance of residual infection as the efficacy end-point. Are these animal models predictive of clinical efficacy, pharmacology and toxicity of an antifungal drug? No single model should be relied upon, as different models of aspergillosis in mice or other animals sometimes show somewhat different results. However, the accumulated wealth of experience has demonstrated the utility of these models in predicting clinical efficacy, pharmacology and toxicity.

Fungal antigens expressed during invasive aspergillosis.

Rabbits that had been infected intravenously with conidiospores of Aspergillus fumigatus were used as sources of antibody for screening a lambda phage cDNA expression library. The cDNA was derived from A. fumigatus mRNA that had been extracted from newly formed, germling hyphae. Thirty-six antigens were identified using antisera from six rabbits. Though many of these antigens were expected to be intracellular proteins because their genes did not encode a signal sequence, the antisera showed consistently a stronger immunoblot reaction with a cell fraction enriched for the fungal cell wall than with a fraction of predominantly intracellular components. Antibodies to eight antigens, including the glycosylhydrolase Asp f 16, were produced by more than one rabbit. In current vaccine studies, Asp f 16 is the only single antigen which has been reported to be capable of inducing protection against invasive aspergillosis in mice. Enolase and Aspergillus HSP90 were detected also; their homologues in Candida albicans have been tested as vaccines and have been reported to provide a partially protective response against invasive candidiasis in mice. The Aspergillus antigens reported here may have value both in diagnostic tests for different forms of aspergillosis and as vaccine candidates for protection against invasive disease.

Gene expression in a murine model of aspergillosis

RATIONALE:Aspergillus fumigatus (Af) antigen exposure results in the development of comparable features of allergic bronchopulmonary aspergillosis in mice. The induction of the disease leads to a number of pathophysiological changes and events. The response to antigen is a complex process and involves alterations in the expression of a number of genes. Gene expression profile from the lungs of mice exposed to Af allergens may provide a better understanding of the pathogenesis of the disease. In this study, we have evaluated the gene expression in the lungs of mice exposed to Af antigens.