Environmental Factors Modify the Severity of Acute DSS Colitis in Caspase-11-Deficient Mice

Ting-Jia Fan1,2, Sandrine Y Tchaptchet2, Diana Arsene2,3

  • 1Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Abstract

Insights

Caspase-11 (Casp11) does not affect chronic colitis severity in mice. Its impact on acute colitis varies with environmental factors like gut microbiota, particularly Clostridiales.

Area of Science:

  • Immunology
  • Microbiology
  • Gastroenterology

Background:

  • The inflammasome plays a role in inflammatory bowel diseases, but its precise function in mouse models is variable.
  • Caspase-11 (Casp11), a noncanonical inflammasome activator, has been reported to attenuate acute dextran sodium sulfate (DSS) colitis.
  • The influence of Casp11 on chronic colitis and the factors affecting its role in acute DSS colitis remain unclear.

Purpose of the Study:

  • To investigate the role of Casp11 in chronic experimental colitis and acute DSS colitis mouse models.
  • To determine the impact of Casp11 on colitis severity in Il10-/- mice and DSS-induced colitis.
  • To explore the relationship between Casp11, the gut microbiome, and colitis.

Main Methods:

  • Assessed Casp11 mRNA levels in colonic tissue using quantitative polymerase chain reaction.
  • Quantified colitis severity through weight loss, histological scoring, IL-12/23p40 secretion, and fecal lipocalin-2 levels.
  • Analyzed fecal microbial composition using 16S amplicon sequencing.

Main Results:

  • Colonic Casp11 mRNA was elevated in Il10-/- mice with chronic colitis but not in DSS colitis models.
  • Casp11 presence did not alter the severity of chronic colitis in either DSS-treated or Il10-/- mice.
  • Initial observations suggested Casp11 exacerbates acute DSS colitis, but subsequent experiments showed no effect, coinciding with significant, stochastic changes in the fecal microbiome, particularly Clostridiales.

Conclusions:

  • Caspase-11 (Casp11) does not influence the severity of chronic experimental colitis.
  • The effects of Casp11 on acute DSS colitis are variable and influenced by environmental factors, notably the gut microbiota composition.
  • Stochastic shifts in the intestinal microbiome, even within the same facility, must be considered when interpreting results from acute DSS colitis studies.

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