Effect of ochratoxin A on the intestinal mucosa and mucosa-associated lymphoid tissues in broiler chickens

The immunotoxic effect of ochratoxin A (OTA) on the intestinal mucosa-associated lymphoid tissue and its cytotoxic action on the intestinal epithelium were studied in broiler chickens experimentally treated with the toxin. From the 7th day of life, 80 male broiler chickens (Ross 308) were randomly divided into four groups of 20 birds each. The three experimental groups (E1-3) were treated with OTA for 28 days (E1: 50 μg/kg body weight [bw]/day; E2: 20 μg/kg bw/day; E3: 1 μg/kg bw/day) and the fourth group served as control. Histological examination of the intestinal mucosa and immunohistochemical staining for identification of CD4+, CD8+, TCR1 and TCR2 lymphocytes in the duodenum, jejunum and ileocaecal junction were performed, and CD4+/CD8+ and TCR1/TCR2 ratios were calculated. OTA toxicity resulted in decreased body weight gain, poorer feed conversion ratio, lower leukocyte and lymphocyte count, and altered intestinal mucosa architecture. After 14 days of exposure to OTA, immunohistochemistry showed a significant reduction of the lymphocyte population in the intestinal epithelium and the lamina propria. After 28 days of exposure, an increase in the CD4+ and CD8+ values in both the duodenum and jejunum of chickens in Groups E1 and E2 was observed, but the TCR1 and TCR2 lymphocyte counts showed a significant reduction. No significant changes were observed in Group E3. The results indicate that OTA induced a decrease in leukocyte and lymphocyte counts and was cytotoxic to the intestinal epithelium and the mucosa-associated lymphoid tissue, altering the intestinal barrier and increasing susceptibility to various associated diseases

BG1 has a major role in MHC-linked resistance to malignant lymphoma in the chicken

Pathogen selection is postulated to drive MHC allelic diversity at loci for antigen presentation. However, readily apparent MHC infectious disease associations are rare in most species. The strong link between MHC-B haplotype and the occurrence of virally induced tumors in the chicken provides a means for defining the relationship between pathogen selection and MHC polymorphism. Here, we verified a significant difference in resistance to gallid herpesvirus-2 (GaHV-2)-induced lymphomas (Marek's disease) conferred by two closely-related recombinant MHC-B haplotypes. We mapped the crossover breakpoints that distinguish these haplotypes to the highly polymorphic BG1 locus. BG1 encodes an Ig-superfamily type I transmembrane receptor-like protein that contains an immunoreceptor tyrosine-based inhibition motif (ITIM), which undergoes phosphorylation and is recognized by Src homology 2 domain-containing protein tyrosine phosphatase (SHP-2). The recombinant haplotypes are identical, except for differences within the BG1 3′-untranslated region (3′-UTR). The 3′-UTR of the BG1 allele associated with increased lymphoma contains a 225-bp insert of retroviral origin and showed greater inhibition of luciferase reporter gene translation compared to the other allele. These findings suggest that BG1 could affect the outcome of GaHV-2 infection through modulation of the lymphoid cell responsiveness to infection, a condition that is critical for GaHV-2 replication and in which the MHC-B haplotype has been previously implicated. This work provides a mechanism by which MHC-B region genetics contributes to the incidence of GaHV-2-induced malignant lymphoma in the chicken and invites consideration of the possibility that similar mechanisms might affect the incidence of lymphomas associated with other oncogenic viral infections