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An Early Life Mucosal Insult Temporarily Decreases Acute Oxazolone-Induced Inflammation in Mice

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Abstract

Inflammatory priming of immune cells in early life may optimize the response to a subsequent inflammatory challenge later in life. To prime the immune cells in the gut in vivo through a short inflammatory insult, we administered a low dose of dextran sulfate sodium (DSS) to 5-weeks-old BALB/c mice in the drinking water. We hypothesized that DSS-primed mice would show decreased inflammation and difference in immunological profiling, when subjected to presensitizing and oxazolone-induced colitis by rectal instillation at 9 weeks compared to non-DSS-primed control mice. In fact, this low-dose DSS priming apparently decreased the acute inflammation, as colitis scores along with IFNγ, IL-1ß, and IL-4 were significantly decreased with the same tendency for IL-5, TNFα, and IL-2 on day 3 post-induction compared to control mice. On day 7, both DSS-primed and control mice had significantly higher numbers of FoxP3+CD8+ regulatory T cells, while they did not differ in any inflammation parameters. No significant differences were found for intraepithelial lymphocytes or mesenteric lymphocytes at any time point after colitis induction. In conclusion, the priming did decrease local acute tissue inflammation of the colon in this commonly applied mouse model of T helper cell type 2-dominated model of inflammatory bowel disease.

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Notes

  1. Candidatus Savagella is the correct name for segmented filamentous bacteria (SFB) in mammals. Candidatus Arthromitus was the original name for all SFBs, and therefore, this is the name, which frequently appears from the databases after sequencing. However, Candidatus Arthromitus are related to Lachnospiraceae and only found in arthropods, while Candidatus Savagella are related to Clostridiaceae and are only found in vertebrates [34].

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Funding

The study was funded by the Novo Nordisk Life Pharm In Vivo Pharmacology Centre (www.lifepharm.dk) and Gut, Grain and Greens (www.3g-center.dk) under the Danish Innovation Fund. Funders did not take part in planning, performing, or publishing.

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Authors and Affiliations

  1. Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Thorvaldsensvej 57, DK-1871, Frederiksberg C, Denmark

    Katja M. Bendtsen, Peter Tougaard & Axel K. Hansen

Authors
  1. Katja M. Bendtsen
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  2. Peter Tougaard
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  3. Axel K. Hansen
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Contributions

KMB: data collection, analysis, and manuscript; PT: FACS, AKH: data analysis and manuscript.

Corresponding author

Correspondence to Axel K. Hansen.

Ethics declarations

The study was carried out in accordance with Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes, as well as the Danish Animal Experimentation Act (LBK 474 15/05/2014). Specific approval was granted by the Animal Experiments Inspectorate under the Ministry of Environment and Food in Denmark.

Conflict of Interest

The authors declare that they have no conflict of interests.

Electronic Supplementary Material

Supplementary Figure 1

Subcategories of colitis scores. The test mice were pre-treated with 1.5% DSS in age-week five, sensitized in age-week nine, induced with oxazolone five days later, and evaluated on day 3 and 7 post-colitis induction (DSS-Oxa), and compared to control mice with no pre-treatment with DSS (Oxa). The figure visualizes the number of mice given each score within the subcategories. (GIF 287 kb)

High resolution image (TIFF 1658 kb)

Supplementary table 1

(DOCX 15 kb)

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Bendtsen, K.M., Tougaard, P. & Hansen, A.K. An Early Life Mucosal Insult Temporarily Decreases Acute Oxazolone-Induced Inflammation in Mice. Inflammation 41, 1437–1447 (2018). https://doi.org/10.1007/s10753-018-0790-y

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