Immunological effects of reduced mucosal
integrity in the early life of BALB/c mice
Katja Maria Bendtsen1*, Camilla Hartmann Friis Hansen1, èukasz Krych2,
Kerstin Skovgaard3, Witold Kot4, Finn Kvist Vogensen2, Axel Kornerup Hansen1
1 Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health
and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, 2 Department of Food Science,
Faculty of Sciences, University of Copenhagen, Copenhagen, Denmark, 3 Section for Immunology and
Vaccinology, National Veterinary Institute, Technical University of Denmark, Copenhagen, Denmark,
4 Department of Environmental Science, Aarhus University, Roskilde, Denmark
Abstract
Certain stimuli at the gut barrier may be necessary in early life to establish a proper balance
of immune tolerance. We evaluated a compromised barrier in juvenile mice in relation to
microbiota and local and systemic immunity. BALB/c mice were treated with a low dose of
dextran sulfate sodium (DSS) with or without ampicillin and lipopolysaccharide (LPS) to clarify
the importance of microbial antigens and interaction between microbial-associated patterns
and toll-like receptors. The barrier breach resulted in increased plasma LPS, which
was highest in mice treated simultaneously with ampicillin. Adding LPS in the food reduced
its levels in plasma. Regulatory T cells were acutely increased in mesenteric lymph nodes
(MLN) and spleen during DSS treatment regardless of simultaneous ampicillin treatment. In
contrast, NK T and NK cells decreased in MLN and in spleen. This acute DSS effect was
reflected in fold changes of haptoglobin and Il1a in colon, and this was also more pronounced
in mice simultaneously treated with ampicillin. On day 1 post-treatment, major
upregulations of Ifng, Foxp3, Il1b, Il2, and Il6 genes in colon were only observed in the mice
simultaneously treated with ampicillin. A two-fold upregulation of colonic Foxp3 and Il1a was
evident 25 days post-treatment. DSS skewed the microbiota in favor of Gram negative
phyla. Therefore, increased permeability induced tolerogenic immunity independent of
microbiota, and this was enhanced by LPS stimulation.
PLOS One doi: 10.1371/journal.pone.0176662