Occurrence of spontaneous tumours of the renal proximal tubules in oscars Astronotus ocellatus

This report describes the occurrence of renal papillary cystic adenomas and adenocarcinomas in oscars Astronotus ocellatus Cuvier, 1829. Samples from 5 oscars with abdominal swelling were collected between 1996 and 2004 and compared to a published case from the USA. Macroscopically, all cases revealed a large, well-demarcated, greyish-brown nodular mass in a retroperitoneal position within the body cavity, and originating from the posterior kidney. Histologically, these neoplasms were composed of epithelial cells, which were arranged in papillary cystic tubular structures and partly covered by cilia. In this study, microscopic and ultrastructural examination confirmed that the origin of the neoplasm was the proximal tubules of the kidney

Oocyst-Derived Extract of Toxoplasma Gondii Serves as Potent Immunomodulator in a Mouse Model of Birch Pollen Allergy.

INTRODUCTION:Previously, we have shown that oral infection with Toxoplasma gondii oocysts prevented type I allergy in mice. Here we investigated whether the application of a T. gondii oocyst lysate antigen (OLA) could also reduce allergy development. BALB/c mice were immunised twice with OLA followed by sensitisation with the major birch pollen (BP) allergen Bet v 1 and an aerosol challenge with BP extract. METHODS:First, we tested OLA in vitro. Stimulation of splenocytes and bone marrow-derived dendritic cells (BMDC) with OLA led to the production of pro-inflammatory and regulatory cytokines such as IL-6, IFN-γ and IL-10. Moreover, BMDC exposed to OLA upregulated the maturation markers CD40, CD80, CD86, and MHCII. Furthermore, OLA was recognised by TLR2-transfected human embryonic kidney cells. RESULTS:Immunisation of mice with OLA induced high levels of Toxoplasma-specific IgG antibodies in sera along with increased production of IFN-γ and IL-10 in Toxoplasma-antigen restimulated splenocytes. OLA reduced allergic airway inflammation as manifested by significant reduction of eosinophils in bronchoalveolar fluids, decreased cellular infiltrates and mucus production in the lungs. Accordingly, Bet v 1-specific IgE was decreased in OLA-pretreated mice. The reduced allergic immune responses were accompanied by increased numbers of CD4+CD25highFoxp3+ regulatory T cells in spleens as well as by increased numbers of granulocytic myeloid-derived suppressor cells in lungs when compared to sensitised controls suggesting that these two cell populations might be involved in the suppression of the allergic immune responses. CONCLUSION:Our data demonstrate that pretreatment with the oocyst extract can exert anti-allergic effects comparable to T. gondii infection. Thus, the immunomodulatory properties of the parasite extract indicate that this extract and in the future defined molecules thereof might serve as immunomodulatory adjuvants in allergy treatment and prophylaxis

Toxoplasma gondii tachyzoite-extract acts as a potent immunomodulator against allergic sensitization and airway inflammation

Abstract Epidemiological and experimental studies have shown an inverse relationship between infections with certain parasites and a reduced incidence of allergic diseases. We and others have shown that infection with Toxoplasma gondii prevents the development of allergy in mice. To establish whether this beneficial effect could be recapitulated by soluble products of this parasite, we tested an extract derived from T. gondii tachyzoites. Immunization of BALB/c mice with tachyzoites lysate antigen (TLA) elicited mixed Th1/Th2 responses. When TLA was applied together with the sensitizing ovalbumin (OVA), the development of allergic airway inflammation was reduced, with decreased airway hyperresponsiveness associated with reduced peribronchial and perivascular cellular infiltration, reduced production of OVA-specific Th2 cytokines in lungs and spleens and reduced levels of serum OVA-specific IgG1 as well as IgE-dependent basophil degranulation. Of note, TLA retained its immunomodulatory properties, inducing high levels of IL-6, TNFα, IL-10 and IL-12p70 in bone marrow-derived dendritic cells after heat-inactivation or proteinase K-treatment for disruption of proteins, but not after sodium metaperiodate-treatment that degrades carbohydrate structures, suggesting that carbohydrates may play a role in immunomodulatory properties of TLA. Here we show that extracts derived from parasites may replicate the benefits of parasitic infection, offering new therapies for immune-mediated disorders

Oesophagostomum dentatum extract modulates T cell-dependent immune responses to bystander antigens and prevents the development of allergy in mice.

One third of the human population is currently infected by one or more species of parasitic helminths. Certain helminths establish long-term chronic infections resulting in a modulation of the host's immune system with attenuated responsiveness to "bystander" antigens such as allergens or vaccines. In this study we investigated whether parasite-derived products suppress the development of allergic inflammation in a mouse model. We show that extract derived from adult male Oesophagostomum dentatum (eMOD) induced Th2 and regulatory responses in BALB/c mice. Stimulation of bone marrow-derived dendritic cells induced production of regulatory cytokines IL-10 and TGF-beta. In a mouse model of birch pollen allergy, co-administration of eMOD with sensitizing allergen Bet v 1 markedly reduced the production of allergen-specific antibodies in serum as well as IgE-dependent basophil degranulation. Furthermore, eMOD prevented the development of airway inflammation, as demonstrated by attenuation of bronchoalveolar lavages eosinophil influx, peribronchial inflammatory infiltrate, and mucus secretion in lungs and IL-4 and IL-5 levels in lung cell cultures. Reduced secretion of Th2-related cytokines by birch pollen-re-stimulated splenocytes and mesenteric lymph node cells was observed in eMOD-treated/sensitized and challenged mice in comparison to sensitized and challenged controls. The suppressive effects of eMOD were heat-stable. Immunization with model antigens in the presence of eMOD reduced production of antibodies to thymus-dependent but not to thymus-independent antigen, suggesting that suppression of the immune responses by eMOD was mediated by interference with antigen presenting cell or T helper cell function but did not directly suppress B cell function. In conclusion, we have shown that eMOD possesses immunomodulatory properties and that heat-stable factors in eMOD are responsible for the dramatic suppression of allergic responses in a mouse model of type I allergy. The identification and characterization of parasite-derived immune-modulating molecules might have potential for designing novel prophylactic/therapeutic strategies for immune-mediated diseases

Allergen-specific antibody levels.

<p>The release of functional Bet v 1-specific IgE was quantified by β-hexosaminidase release from rat basophil leukaemia cells (RBL) (A). Bet v 1-specific IgG1 (B) and IgG2a (C) antibody levels were measured by ELISA. Antibody isotypes were determined in sera collected on day 49. Results represent pooled values from three independent experiments with four to eight mice per group. * <i>p</i> < 0.05; *** <i>p</i> < 0.001.</p

Treatment schedule.

<p>Mice were either infected orally with <i>T</i>. <i>gondii</i> oocysts on day 0 or immunised intraperitoneally with the oocyst lysate antigen OLA on day 0 and day 6. Sensitised controls and sham controls received GERBU/PBS on day 0 and day 6. Thereafter <i>T</i>. <i>gondii</i>-infected, OLA-pretreated and sensitised control mice were sensitised by three subcutaneous injections with the major birch pollen allergen r Bet v 1/Alum on day 10, 24 and 38 followed by an aerosol challenge with birch pollen extract on days 45 and 46. Sham controls received PBS/Alum on day 10, 24 and 38 and PBS on day 45 and 46. The experiment was terminated on day 49.</p

Allergic airway inflammation.

<p>Bronchoalveolar lavage fluids (BALF) were collected on day 49 and differential cell counts (total cells, macrophages, lymphocytes, neutrophils and eosinophils) were performed after H&E staining of cytospins (A). BALF cell counts represent pooled values from two independent experiments with five to eight mice per group. Representative H&E-stained BALF cells with arrows (↑) indicating eosinophils at a 100 x magnification from one representative experiment out of three (B). Representative lung tissue sections stained with H&E and Periodic Acid Schiff (PAS) at x 40 magnification. Lung histopathology scores were evaluated from two independent experiments and are presented as pooled values (C). IL-13 (D) levels were determined by ELISA in BALF sampled from two independent experiments with four to eight mice. IL-4 (E) and IL-5 (F) production was measured in supernatants of birch pollen restimulated lung cells by ELISA from three independent experiments with four to eight mice. Results represent pooled values. * <i>p</i> < 0.05; ** <i>p</i> < 0.01; *** <i>p</i> < 0.001.</p

Brain cyst counts and parasite-specific antibody and cytokine production.

<p>Brain cysts were counted on day 49 (A). Results represent pooled values from two independent experiments with four to eight mice per group. <i>Toxoplasma</i>-specific IgG antibodies were measured in sera (B). IL-10 (C) and IFN-γ (D) production was determined in <i>Toxoplasma</i>-stimulated splenocytes <i>in vitro</i>. Spleens and sera were sampled on day 49. Results represent pooled values from three independent experiments with four to eight mice per group. * <i>p</i> < 0.05; ** <i>p</i> < 0.01; *** <i>p</i> < 0.001.</p

Cytokine production in splenocytes and BMDC and maturation of BMDC.

<p>Splenocytes (A) and BMDC (B) derived from naive BALB/c mice were stimulated with OLA or cultured with medium alone. IFN-γ, IL-6 and IL-10 levels were determined in supernatants by ELISA. Results show pooled values ± SEM of three to four independent experiments performed with cell suspensions prepared from one individual mouse per experiment. * <i>p</i> < 0.05; ** <i>p</i> < 0.01; *** <i>p</i> < 0.001. BMDC cultured with Pam3Cys, LPS, OLA or medium alone were analysed by flow cytometry for the expression of the maturation markers CD40, CD80, CD86 and MHCII after gating on CD11c⁺ cells (C). Representative histograms from one out of three repeated experiments.</p

Oocyst-Derived Extract of <i>Toxoplasma Gondii</i> Serves as Potent Immunomodulator in a Mouse Model of Birch Pollen Allergy

<div><p>Introduction</p><p>Previously, we have shown that oral infection with <i>Toxoplasma gondii</i> oocysts prevented type I allergy in mice. Here we investigated whether the application of a <i>T</i>. <i>gondii</i> oocyst lysate antigen (OLA) could also reduce allergy development. BALB/c mice were immunised twice with OLA followed by sensitisation with the major birch pollen (BP) allergen Bet v 1 and an aerosol challenge with BP extract.</p><p>Methods</p><p>First, we tested OLA <i>in vitro</i>. Stimulation of splenocytes and bone marrow-derived dendritic cells (BMDC) with OLA led to the production of pro-inflammatory and regulatory cytokines such as IL-6, IFN-γ and IL-10. Moreover, BMDC exposed to OLA upregulated the maturation markers CD40, CD80, CD86, and MHCII. Furthermore, OLA was recognised by TLR2-transfected human embryonic kidney cells.</p><p>Results</p><p>Immunisation of mice with OLA induced high levels of <i>Toxoplasma</i>-specific IgG antibodies in sera along with increased production of IFN-γ and IL-10 in <i>Toxoplasma</i>-antigen restimulated splenocytes. OLA reduced allergic airway inflammation as manifested by significant reduction of eosinophils in bronchoalveolar fluids, decreased cellular infiltrates and mucus production in the lungs. Accordingly, Bet v 1-specific IgE was decreased in OLA-pretreated mice. The reduced allergic immune responses were accompanied by increased numbers of CD4⁺CD25^highFoxp3⁺ regulatory T cells in spleens as well as by increased numbers of granulocytic myeloid-derived suppressor cells in lungs when compared to sensitised controls suggesting that these two cell populations might be involved in the suppression of the allergic immune responses.</p><p>Conclusion</p><p>Our data demonstrate that pretreatment with the oocyst extract can exert anti-allergic effects comparable to <i>T</i>. <i>gondii</i> infection. Thus, the immunomodulatory properties of the parasite extract indicate that this extract and in the future defined molecules thereof might serve as immunomodulatory adjuvants in allergy treatment and prophylaxis.</p></div