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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-015-0223-y) contains supplementary material, which is available to authorized users.