Modulation of the spleen transcriptome in domestic turkey (Meleagris gallopavo) in response to aflatoxin B1 and probiotics.

Poultry are highly susceptible to the immunotoxic effects of the food-borne mycotoxin aflatoxin B1 (AFB1). Exposure impairs cell-mediated and humoral immunity, limits vaccine efficacy, and increases the incidence of costly secondary infections. We investigated the molecular mechanisms of AFB1 immunotoxicity and the ability of a Lactobacillus-based probiotic to protect against aflatoxicosis in the domestic turkey (Meleagris gallopavo). The spleen transcriptome was examined by RNA sequencing (RNA-seq) of 12 individuals representing four treatment groups. Sequences (6.9 Gb) were de novo assembled to produce over 270,000 predicted transcripts and transcript fragments. Differential expression analysis identified 982 transcripts with statistical significance in at least one comparison between treatment groups. Transcripts with known immune functions comprised 27.6 % of significant expression changes in the AFB1-exposed group. Short exposure to AFB1 suppressed innate immune transcripts, especially from antimicrobial genes, but increased the expression of transcripts from E3 ubiquitin-protein ligase CBL-B and multiple interleukin-2 response genes. Up-regulation of transcripts from lymphotactin, granzyme A, and perforin 1 could indicate either increased cytotoxic potential or activation-induced cell death in the spleen during aflatoxicosis. Supplementation with probiotics was found to ameliorate AFB1-induced expression changes for multiple transcripts from antimicrobial and IL-2-response genes. However, probiotics had an overall suppressive effect on immune-related transcripts.

[Poisoning with the brown roll-rim mushroom, Paxillus involutus]. / Forgiftning med svampen almindelig netbladhat, Paxillus involutus.

Brown Roll-Rim (Paxillus involutus) is a dangerous poisonous mushroom with symptoms of poisoning which occur a few hours after consumption. Repeated consumption may cause sensitization to a heat-stable toxin, resulting in haemolysis which may be of all degrees. In addition, severe gastrointestinal symptoms may be due to a heat-instable toxin. In cases with immune haemolysis, treatment consists of corticosteroid and possibly plasmapheresis and symptomatic therapy.

[Biochemical, hematological and immunological criteria for assessing chronic T-2 mycotoxicosis in mice]. / Biokhimicheskie, gematologicheskie i immunologicheskie kriterii otsenki khronicheskogo T-2 mikotoksikoza u myshei.

The authors studied the effect of a long-term intragastric administration to CBA X C57Bl/6 male mice of T-2 toxin in doses of 0.067 mg/kg bw a day (1/100 of the LD50) or 0.33 and 0.45 mg/kg a day (1/20 and 1/15 of the LD50) on the liver content of protein, cytochrome P-450 SH-glutathione and on the activity of 10 lysosomal and microsomal enzymes and glutathione transferase. A dose-dependent increase in the activity of lysosomal hydrolases and glutathione transferase localized in cytosol was revealed together with a fall in the activity of microsomal aniline hydroxylase, carboxyl esterase and epoxide hydrolase. Emphasis is laid on a dose-dependent reduction in the liver of nonsedimented activity of lysosomal enzymes. In T-2 mycotoxicosis, the most sensitive and the most stable parameter was the activity of lysosomal enzymes in blood serum. That activity also declined during the recovery period, namely 3 months after discontinuance of toxin administration. Both groups of mice showed a progressive decrease in the blood leukocyte count and lysozyme content, whereas in the spleen, there was a decrease in the number of antibody-forming cells. It is concluded that biochemical, hematological and hematological characteristics should be taken into consideration in evaluating the chronic action of T-2 toxin.

Severe hemolysis caused by antibodies against the mushroom Paxillus involutus and its therapy by plasma exchange.

It has been shown that fatal "poisoning" with the mushroom species Paxillus involutus is caused by antibodies against the fungus in sensitized patients. Because circulating immune complexes play an important role, therapeutic procedures which can eliminate those complexes could stop immune hemolysis. A 37-year-old patient became severely ill after repeated ingestion of sufficiently cooked Paxillus involutus. As a result of hemolysis with reversible shock symptoms, acute renal failure developed. Plasma exchange with 3,000 ml albumin 5% was carried out daily during the first 3 days after admission. Each plasma exchange lowered free hemoglobin and immune complex levels by 60%-75%. Acute renal failure was successfully treated with hemodialysis. Specific IgG-antibodies against membrane particles of Paxillus involutus were detected by hemagglutination tests in the serum of the patient. The sequence of reactions resulting from the testing procedures strongly suggests the formation of immune complexes. These complexes are likely to bind to erythrocytes acting as innocent bystanders. Activation of the complement system finally results in hemolysis and shock. In addition to adequate shock treatment elimination of these immune complexes by plasma separation seems to be the therapy of choice.

[Hemolysis in mushroom poisoning: facts and hypotheses]. / Hämolyse bei Pilzvergiftungen: Fakten und Hypothesen.

Primary hemolysis induced by antigens and toxins of mushrooms must be distinguished from hemolysis secondary to shock and disseminated intravascular coagulation with disruption of erythrocytes caused by severe poisoning with many mushroom species. Primary hemolysis is well documented as immunohemolysis after repeated ingestion of involute paxillus (Paxillus involutus). Direct hemolysis is reported after eating raw mushrooms with a high content of hemolysins. Hemolysis is only speculative in monomethylhydrazine poisoning by false morels (Gyromitra esculenta). Secondary hemolysis due to shock is not uncommon. Hemolysis in connection with enzymopenia of erythrocytes has not been documented as yet. In the present study the various hemolytic syndromes are described and discussed.

[Immunological activity of the blood sera from cattle with chronic mycotoxicosis]. / Imunologichna aktivnost na kruvni serumi ot goveda s khronichna mikotoksikoza.

Attempts were made to disclose and reproduce the immunologic activity of the blood sera of cows, aborted fetuses, and newborn calves in feeding the cows with feeds acted upon by small amounts of toxic moulds. Studied were blood samples of cows in advanced pregnancy or such that had freshly calved, of cows with liver dystrophy, and of newborn calves with toxic dyspepsia. The methods of immunodiffusion and immunoelectrophoresis were employed. It was found that in continuous feeding with mould-affected forages the toxins that gained access into the body attacked chiefly the liver. Along with other changes it induced the release of a complex antigen that was likely to bear the character of both the toxin and the liver proteins. It is believed that the process of building up of specific immune defense against mycotoxins is more complex and continuous. Thus, the immunity obtained is not so effective as in the case of microbial infections.

Increased levels of soluble complement receptor 1 in serum patients with liver diseases.

Complement receptor type 1 (CR1) is an integral membrane protein of many hematopoietic cells and is found in a soluble form in plasma. Preliminary data have indicated that soluble complement receptor 1 (sCR1) levels in serum were increased in patients with cirrhosis. In this study, sCR1 was measured in patients with various liver diseases with a newly established enzyme-linked immunosorbent assay (ELISA). sCR1 level was elevated in chronic active hepatitis C (24 patients, 62.6 +/- 31 ng/ML; 31 normal controls, 31.4 +/- 7.8 ng/mL, P < .001), and in cirrhosis (35 patients, 143.7 +/- 61 ng/mL, P < .001). The levels increased transiently in 3 patients who had amanita phalloides intoxication. In 25 patients with advanced cirrhosis (pretransplantation screening), there were significant inverse correlations between sCR1 and both the prothrombin index (rs = -.60, P < .002) and the aminopyrine breath test (rs = -.51, P < .01). Following liver transplantation, the levels dropped from 166 +/- 70 to 49 +/- 24 ng/mL (P < .0001), and serial measurements in the posttransplantation period showed a correlation with liver dysfunction, regardless of etiology. Since CR1 is not produced by hepatocytes, the most likely explanation for the increased level of sCR1 is reduced is reduced catabolism. Thus, sCR1 may be added to the short list of large glycoproteins that accumulate in liver disease.