Enterococcus faecium NCIMB 10415 supplementation affects intestinal immune-associated gene expression in post-weaning piglets.
In a Salmonella challenge study of weaned piglets supplemented with the probiotic Enterococcus faecium NCIMB 10415 (SF68), we observed a delayed, post-infection proliferative response of purified blood mononuclear cell fractions towards Salmonella antigens. In order to clarify this observation, we examined the patterns of immune-associated gene expression in long-term feeding trials of both pre- and post-weaning piglets. Piglets supplemented with E. faecium NCIMB 10415 showed a post-weaning dysregulation in the expression patterns of both pro- and anti-inflammatory cytokine expression in intestinal tissues and spleen. Piglets of the supplemented group showed significantly reduced levels of IL-8, IL-10 and the co-stimulatory molecule CD86 mRNA expression in ileal Peyer's patches. The expression of CTLA4, an inhibitor of T-cell activation/proliferation, showed similar levels of expression in all tissues examined, particularly in ileal Peyer's patches post-weaning where IL-8, IL-10 and CD86 transcript levels were significantly reduced relative to control animals. Blood serum cytokine protein levels showed elevated TGFβ in pre-weaning piglets which, together with IL-6, may have suppressed IFNγ production in the probiotic-fed animals. In a second Salmonella challenge study, post-weaning, E. faecium-fed animals showed significantly elevated levels of IL-8 gene expression in mesenteric lymph nodes, but reduced levels in the spleen. At early times post-infection, the probiotic-fed group showed similar levels of IL-10, CD86 and CTLA4 mRNA expression as the control animals in intestinal Peyer's Patches, despite high relative levels of IL-8 expression in mesenteric lymph nodes. The sum of the observations suggests that supplementation of pre-weaning piglets with E. faecium affects intestinal immune-associated gene expression, which is aggravated post-weaning when the animals receive increased levels of the probiotic in feed. We suggest the post-weaning reductions in gene expression may delay the host response to infections, and provide pathogenic bacteria such as Salmonella with a "window of opportunity", leading to the increased bacterial loads and shedding observed in challenge trials. Possible mechanisms explaining these effects of E. faecium NCIMB 10415 are discussed.
Institute of Microbiology and Epizootics, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany.
Bianca
B
Siepert
Institute of Microbiology and Epizootics, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany; Institute of Anatomy, Medical Faculty, Otto-von-Guericke Universität, Leipziger Str. 44, 39120 Magdeburg, Germany.
Nicole
N
Reinhardt
Breeding Biology and Molecular Genetics, Humboldt-Universität zu Berlin, Invalidenstrasse 42, 10115 Berlin, Germany.
Susanne
S
Kreuzer
Institute of Veterinary Biochemistry, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany.
Angelika
A
Bondzio
Molecular Biology and Bioinformatics, Charité University Medicine, Arnimallee 22, 14195 Berlin, Germany.
Sven
S
Twardziok
Breeding Biology and Molecular Genetics, Humboldt-Universität zu Berlin, Invalidenstrasse 42, 10115 Berlin, Germany.
Gudrun
G
Brockmann
Federal Institute for Risk Assessment, Diedersdorfer Weg 1, 12277 Berlin, Germany.
Karsten
K
Nöckler
Federal Institute for Risk Assessment, Diedersdorfer Weg 1, 12277 Berlin, Germany.
Istvan
I
Szabó
Federal Institute for Risk Assessment, Diedersdorfer Weg 1, 12277 Berlin, Germany.
Pawel
P
Janczyk
Institute of Animal Nutrition, Freie Universität Berlin, Königin-Luise-Str. 49, 14195 Berlin, Germany.
Robert
R
Pieper
Institute of Microbiology and Epizootics, Freie Universität Berlin, Robert-von-Ostertag-Str. 7-13, 14163 Berlin, Germany. Electronic address: karsten.tedin@fu-berlin.de.
Karsten
K
Tedin
D000818:Animals; D016207:Cytokines / Q000097:blood / Q000276:immunology; D016984:Enterococcus faecium / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D005260:Female; D020869:Gene Expression Profiling / Q000662:veterinary; D007410:Intestinal Diseases / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control / Q000662:veterinary*; D011247:Pregnancy; D019936:Probiotics / Q000494:pharmacology*; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D013552:Swine; D013553:Swine Diseases / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control
D016207:Cytokines; D012329:RNA, Bacterial
Enterococcus faecium; Innate immunity; Porcine; Probiotics; Salmonella infections