ena-STUDY-UNIVERSITY OF COPENH-16-03-2017-12:58:02:541-139
Immunological Effects of Reduced Mucosal Integrity in the Early Life of BALB/c Mice
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 non-colitis inducing 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. Barrier breach resulted in increasing plasma LPS, with highest level when treated simultaneously with ampicillin. Adding LPS reduced this plasma level. Regulatory T cells increased acutely 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. Acute DSS effect was reflected in fold changes of the expression of haptoglobin and Il1a in colon, and this was more pronounced in mice simultaneously treated with ampicillin. On day 1 posttreatment, major upregulation of Ifng, Foxp3, Il1b, Il2, and Il6 genes in colon was only observed in ampicillin-treated mice in which LPS leakage was also at the highest level. 2-fold upregulation of colonic Foxp3 and Il1a was evident 25 days posttreatment. 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.
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 non-colitis inducing 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. Barrier breach resulted in increasing plasma LPS, with highest level when treated simultaneously with ampicillin. Adding LPS reduced this plasma level. Regulatory T cells increased acutely 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. Acute DSS effect was reflected in fold changes of the expression of haptoglobin and Il1a in colon, and this was more pronounced in mice simultaneously treated with ampicillin. On day 1 posttreatment, major upregulation of Ifng, Foxp3, Il1b, Il2, and Il6 genes in colon was only observed in ampicillin-treated mice in which LPS leakage was also at the highest level. 2-fold upregulation of colonic Foxp3 and Il1a was evident 25 days posttreatment. 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.