F4+ ETEC infection and oral immunization with F4 fimbriae elicits an IL-17-dominated immune response

Abstract

Enterotoxigenic Escherichia coli (ETEC) are an important cause of post-weaning diarrhea (PWD) in piglets. Porcine-specific ETEC strains possess different fimbrial subtypes of which F4 fimbriae are the most frequently associated with ETEC-induced diarrhea in piglets. These F4 fimbriae are potent oral immunogens that induce protective F4-specific IgA antibody secreting cells at intestinal tissues. Recently, T-helper 17 (Th17) cells have been implicated in the protection of the host against extracellular pathogens. However, it remains unknown if Th17 effector responses are needed to clear ETEC infections. In the present study, we aimed to elucidate if ETEC elicits a Th17 response in piglets and if F4 fimbriae trigger a similar response. F4+ ETEC infection upregulated IL-17A, IL-17F, IL-21 and IL-23p19, but not IL-12 and IFN-γ mRNA expression in the systemic and mucosal immune system. Similarly, oral immunization with F4 fimbriae triggered a Th17 signature evidenced by an upregulated mRNA expression of IL-17F, RORγt, IL-23p19 and IL-21 in the peripheral blood mononuclear cells (PBMCs). Intriguingly, IL-17A mRNA levels were unaltered. To further evaluate this difference between systemic and mucosal immune responses, we assayed the cytokine mRNA profile of F4 fimbriae stimulated PBMCs. F4 fimbriae induced IL-17A, IL-17F, IL-22 and IL-23p19, but downregulated IL-17B mRNA expression. Altogether, these data indicate a Th17 dominated response upon oral immunization with F4 fimbriae and F4+ ETEC infection. Our work also highlights that IL-17B and IL-17F participate in the immune response to protect the host against F4+ ETEC infection and could aid in the design of future ETEC vaccines.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-015-0264-2) contains supplementary material, which is available to authorized users.

The fecal presence of enterotoxin and F4 genes as an indicator of efficacy of treatment with colistin sulfate in pigs

“…These findings could be explained by the effective immune response against ETEC: F4 in the challenged groups. Indeed, several studies have shown that oral immunization of weaned piglets with F4 fimbriae induced a systemic F4-specific antibody response and an increase in mucosal F4-specific antibody (IgA, IgM, IgG) in intestinal tissues [26–28]. On the other hand, after the termination of CS oral treatment, the fecal F4-negative ETEC population reappeared in the unchallenged treated group to the same extent as observed in the unchallenged untreated group.…”

Potential immunosuppressive effects of Escherichia coli O157:H7 experimental infection on the bovine host

“…Several pathogens, like gram-positive Propionibacterium acnes and gram-negative Citrobacter rodentium , induce mainly Th17 responses [50]. Furthermore, Luo et al [51] have shown that F4 fimbriae of ETEC can elicit an IL17 response in piglets, suggesting a role in protection of the host against ETEC infection.…”

Animal Enterotoxigenic Escherichia coli

“…Fimbriae-mediated ETEC colonization of the intestines in pigs induces also innate immune responses (127–129), but it is not clear what bacterial molecules are responsible, whether LPS, flagellin or other effectors. The pathogenesis of ETEC strains is specifically linked with the colonization of the small intestine and not of the large intestine.…”