Oral administration of a select mixture of Bacillus probiotics generates Tr1 cells in weaned F4ab/acR- pigs challenged with an F4+ ETEC/VTEC/EPEC strain.

Although breeding of F4 receptor-negative (F4R ^-) pigs may prevent post-weaning diarrhea, the underlying immunity is poorly understood. Here, various doses of a Bacillus licheniformis and Bacillus subtilis mixture (BLS-mix) were orally administered to F4ab/acR ^- pigs for 1 week before F4 (K88) - positive ETEC/VTEC/EPEC challenge. Administration of BLS-mix increased the percentage of Foxp3 ^- IL-10 ⁺ T cells but not of Foxp3 ⁺ IL-10 ⁺ regulatory T (Treg) cells among peripheral blood CD4 ⁺ T cells. A low dose of BLS-mix feeding resulted in increased the expression of IL-6, TNF-α, IL-10, and the transcription factors Foxp3 and T-bet mRNAs in the jejunum. Administration of either a low or high dose BLS-mix also led to an increase in the percentage of CD4 ⁺ Foxp3 ⁺ Treg cells among intraepithelial lymphocytes and CD4 ⁺ IL-10 ⁺ T cells in the small intestinal Peyer's patches and the lamina propria of F4ab/acR ^- pigs following F4 ⁺ ETEC/VTEC/EPEC challenge. The increased number of IL-10-producing CD4 ⁺ T cells was attributed to an increase in the proportion of Foxp3 ^- IL-10 ⁺ Treg cells rather than Foxp3 ⁺ IL-10 ⁺ Treg cells. Our data indicate that oral administration of BLS-mix to newly weaned F4ab/acR ^- pigs ameliorates enteritis in an F4 ⁺ ETEC/VTEC/EPEC model; however, induction of IL-10-producing Foxp3 ^- Treg cells by BLS-mix administration cannot account for the protection of newly weaned F4ab/acR ^- pigs from F4 ⁺ ETEC/VTEC/EPEC infection, and that excessive generation of CD4 ⁺ IL-10 ⁺ T cells following consumption of BLS-mix during episodes of intestinal inflammation that is caused by enteric pathogens might prohibit clearance of the pathogen. Select probiotic mixtures may allow for tailoring strategies to prevent infectious diseases. [ABSTRACT FROM AUTHOR]