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

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.

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.

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.

Perinatal maternal administration of Lactobacillus paracasei NCC 2461 prevents allergic inflammation in a mouse model of birch pollen allergy.

BACKGROUND: The hygiene hypothesis implies that microbial agents including probiotic bacteria may modulate foetal/neonatal immune programming and hence offer effective strategies for primary allergy prevention; however their mechanisms of action are poorly understood. We investigated whether oral administration of Lactobacillus paracasei NCC 2461 to mothers during gestation/lactation can protect against airway inflammation in offspring in a mouse model of birch pollen allergy, and examined the immune mechanisms involved. METHODS: BALB/c mice were treated daily with L. paracasei in drinking water or drinking water alone in the last week of gestation and during lactation. Their offspring were sensitized with recombinant Bet v 1, followed by aerosol challenge with birch pollen extract. RESULTS: Maternal exposure to L. paracasei prevented the development of airway inflammation in offspring, as demonstrated by attenuation of eosinophil influx in the lungs; reduction of IL-5 levels in bronchoalveolar lavage, and in lung and mediastinal lymph node cell cultures; and reduced peribronchial inflammatory infiltrate and mucus hypersecretion. While allergen-specific IgE and IgG antibody levels remained unchanged by the treatment, IL-4 and IL-5 production in spleen cell cultures were significantly reduced upon allergen stimulation in offspring of L. paracasei treated mice. Offspring of L. paracasei supplemented mothers had significantly reduced Bet v 1-specific as well as Concanavalin A-induced responses in spleen and mesenteric lymph node cell cultures, suggesting the modulation of both antigen-specific and mitogen-induced immune responses in offspring. These effects were associated with increased Foxp3 mRNA expression in the lungs and increased TGF-beta in serum. CONCLUSION: Our data show that in a mouse model of birch pollen allergy, perinatal administration of L. paracasei NCC 2461 to pregnant/lactating mothers protects against the development of airway inflammation in offspring by activating regulatory pathways, likely through TLR2/4 signalling.

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.

Poxvirus infection in a great tit (Parus major).

Four great tits (Parus major) with nodular lesions suggestive of poxvirus infections were observed in a garden in Vienna, Austria. One of the birds was submitted for examination. Because of its poor condition, the bird had to be euthanatized and was subsequently necropsied. An avipoxvirus infection was confirmed by histopathology, electron microscopy, and polymerase chain reaction and sequencing. This is the second report of naturally occurring poxvirus infection in great tits and the first of its kind in central Europe.

Physical exercise retards the development of chronic nephropathy in the ageing rat as efficiently as food restriction does.

BACKGROUND: Obesity combined with decreasing physical fitness in the ageing Western populations promotes a number of degenerative diseases, including chronic kidney disease. It has further been shown in rodent models that prevention of obesity by food restriction mitigates development of kidney lesions. Whether lifelong physical activity also has a positive effect is not known. OBJECTIVE: To compare the effects of physical exercise and food restriction on the development of chronic kidney lesions in ageing rats. METHODS: Male Sprague-Dawley rats were divided into groups: voluntarily running in wheels (RW), food restriction to the degree necessary to attain pair weight to RW rats (PW), forced running in treadmills (TM) and sedentary controls housed individually (S1) or 4 in each cage (S4). The interventions began at the age of 5 months and kidneys were sampled and analysed histologically at the ages of 15, 19 and 23 months. RESULTS: Total score for kidney lesions (sum of the scores for glomerular changes, interstitial non-purulent inflammation, proteinaceous casts in tubules and increased amount of connective tissue, the possible maximum being 10.0) increased from 0.5 +/- 0.2 at 5 months of age to 1.6 +/- 0.3 for RW, 2.3 +/- 0.4 for PW, 4.5 +/- 0.4 for TM, 3.6 +/- 0.5 for S1 and 5.4 +/- 0.6 for S4 at the age of 23 months. The increase from 5 months of age was gradual for all groups through 15, 19 and 23 months. The patterns for the various lesions followed the same pattern with the exception of connective tissue, which did not increase. CONCLUSION: Voluntary running in wheels is as effective in mitigating kidney lesions as is food restriction, while forced running in a treadmill is not effective in this respect.

Diagnostic imaging of a renal adenoma in a Red Oscar (Astronotus ocellatus Cuvier, 1829).

This case report describes the radiographic, ultrasonographic and computed tomographic (CT) examination of an abdominal swelling in a Red Oscar (Astronotus ocellatus Cuvier, 1829). While radiography only demonstrated caudoventral compression of the swimbladder, ultrasonography found a huge tumor-like parenchyma in the caudal abdomen. CT studies detected a possible connection between the tumor and the kidneys. Necropsy and pathohistology were performed. A papillary-cystic adenoma of the kidney was diagnosed.