Abstract

Efficient strategies for treating enteritis caused by F4+ enterotoxigenic Escherichia coli (ETEC)/verocytotoxigenic Escherichia coli (VTEC)/enteropathogenic E. coli (EPEC) in mucin 4 resistant (MUC4 RR; supposed to be F4ab/ac receptor–negative [F4ab/acR−]) pigs remain elusive. A low (3.9 × 108 CFU/day) or high (7.8 × 108 CFU/day) dose of Bacillus licheniformis and Bacillus subtilis spore mixture (BLS-mix) was orally administered to MUC4 RR piglets for 1 week before F4+ ETEC/VTEC/EPEC challenge. Orally fed BLS-mix upregulated the expression of TLR4, NOD2, iNOS, IL-8, and IL-22 mRNAs in the small intestine of pigs challenged with E. coli. Expression of chemokine CCL28 and its receptor CCR10 mRNAs was upregulated in the jejunum of pigs pretreated with high-dose BLS-mix. Low-dose BLS-mix pretreatment induced an increase in the proportion of peripheral blood CD4−CD8− T-cell subpopulations and high-dose BLS-mix induced the expansion of CD4−CD8− T cells in the inflamed intestine. Immunostaining revealed that considerable IL-7Rα–expressing cells accumulated at the lamina propria of the inflamed intestines after E. coli challenge, even in pigs pretreated with either low- or high-dose BLS-mix, although Western blot analysis of IL-7Rα expression in the intestinal mucosa did not show any change. Our data indicate that oral administration of the probiotic BLS-mix partially ameliorates E. coli-induced enteritis through facilitating upregulation of intestinal IL-22 and IκBα expression, and preventing loss of intestinal epithelial barrier integrity via elevating ZO-1 expression. However, IL-22 also elicits an inflammatory response in inflamed intestines as a result of infection with enteropathogenic bacteria.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-016-0355-8) contains supplementary material, which is available to authorized users.

Highlights

  • Enterotoxigenic Escherichia coli bearing F4 fimbriae (F4+ enterotoxigenic Escherichia coli (ETEC)) is the most prevalent ETEC strain in causing postweaning diarrhea in pigs [1]

  • We recently found that an F4+ enterotoxigenic E. coli (ETEC)/verocytotoxigenic E. coli (VTEC)/enteropathogenic E. coli (EPEC) hybrid can cause enteritis and/or fever in mucin 4 (MUC4) mucin resistant (RR) pigs

  • Our recent study showed that excessive generation of CD4+ interleukin (IL)-10–positive T cells following consumption of a B. licheniformis and B. subtilis mixture (BLS-mix) during episodes of intestinal inflammation caused by F4+ ETEC/VTEC/EPEC can inhibit clearance of the pathogen in newly weaned MUC4 RR pigs [6]

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Summary

Introduction

Enterotoxigenic Escherichia coli bearing F4 fimbriae (F4+ ETEC) is the most prevalent ETEC strain in causing postweaning diarrhea in pigs [1]. Breeding programs with F4 receptor–negative pigs is preferable for prevention of F4+ ETEC infection, and a polymorphism in the mucin 4 (MUC4) gene has been developed to allow genotyping for determining F4ab/ac ETEC resistance/susceptibility [2, 3]. According to this DNA marker-based test, pigs were. Our recent study showed that excessive generation of CD4+ interleukin (IL)-10–positive T cells following consumption of a B. licheniformis and B. subtilis mixture (BLS-mix) during episodes of intestinal inflammation caused by F4+ ETEC/VTEC/EPEC can inhibit clearance of the pathogen in newly weaned MUC4 RR pigs [6]. Effective defense against F4+ ETEC/VTEC/ EPEC achieved through coordination of complex signaling networks linking the innate and adaptive immune systems remains elusive

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