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Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
Colonic Engyodontium fungus triggers neutrophil antimicrobial activity to suppress Lactobacillus johnsonii-derived
Xinying Wang1,2,3, Haiyang Sun2, Ying Tan2
1Department of Gastroenterology and Hepatology, and.
Abstract:
Isolating commensal fungi from mouse intestines has been challenging, limiting our understanding of their role in intestinal immune homeostasis and diseases. Using an Fc fusion protein of the C-type lectin receptor Dectin-2, we successfully purified the commensal Ascomycota fungus Engyodontium sp. from mouse feces. Engyodontium enhances the antimicrobial activity of colonic neutrophils via the CARD9 pathway and exacerbates colitis by impairing the colonization of intestinal Lactobacillus johnsonii WXY strain. L. johnsonii produces high levels of l-glutamic acid by expressing the glutaminase-encoding gene glsA to facilitate Treg expansion via enhancing IL-2 receptor signaling. Patients with Crohn disease (CD) and ulcerative colitis harbored increased Engyodontium and decreased L. johnsonii abundance. Engyodontium directly induced calprotectin in human colonic neutrophils, and patients with CD had lower levels of l-glutamic acid, which also promoted human Treg expansion. These findings highlight the Engyodontium-calprotectin axis against the Lactobacillus-glutamate-Treg cascade to aggravate colitis, suggesting commensal Engyodontium-triggered signaling as a therapeutic target for mucosal inflammatory diseases.
Insights
Commensal fungi like Engyodontium exacerbate colitis by impairing beneficial Lactobacillus johnsonii. This discovery reveals a new therapeutic target for inflammatory bowel diseases.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Intestinal commensal fungi roles in immune homeostasis and disease remain unclear due to isolation challenges.
- Understanding fungal-bacterial interactions in the gut is crucial for inflammatory bowel disease (IBD) research.
Purpose of the Study:
- To isolate and characterize commensal fungi from the mouse intestine.
- To investigate the role of Engyodontium fungus in colitis and its interaction with Lactobacillus johnsonii.
Main Methods:
- Utilized an Fc fusion protein of Dectin-2 for isolating Engyodontium sp. from mouse feces.
- Investigated the CARD9 pathway's involvement in Engyodontium-induced neutrophil antimicrobial activity.
- Analyzed the impact of Engyodontium on Lactobacillus johnsonii colonization and L-glutamic acid production.
Main Results:
- Successfully isolated Engyodontium sp., revealing its enhancement of colonic neutrophil antimicrobial activity via the CARD9 pathway.
- Demonstrated that Engyodontium exacerbates colitis by reducing Lactobacillus johnsonii colonization, which impairs Treg expansion.
- Observed increased Engyodontium and decreased L. johnsonii in patients with Crohn's disease and ulcerative colitis.
Conclusions:
- The Engyodontium-calprotectin axis counteracts the Lactobacillus-glutamate-Treg cascade, worsening colitis.
- Commensal Engyodontium-triggered signaling presents a potential therapeutic target for mucosal inflammatory diseases like IBD.
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