TY - JOUR

T1 - Immunological effects of reduced mucosal integrity in the early life of BALB/c mice

AU - Bendtsen, Katja Maria Bangsgaard

AU - Hansen, Camilla Hartmann Friis

AU - Krych, Lukasz

AU - Skovgaard, Kerstin

AU - Kot, Witold Piotr

AU - Vogensen, Finn Kvist

AU - Hansen, Axel Kornerup

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0176662

DO - 10.1371/journal.pone.0176662

M3 - Journal article

C2 - 28459871

VL - 12

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 5

M1 - 0176662

ER -