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Clostridioides difficile-Driven Expansion of IL1B+ Monocytes Amplifies Neutrophil Recruitment in Ulcerative Colitis 2258811

Year: 2026
Type: article
Study design: Observational Study
Abstract: Introduction Clostridioides difficile colonization, defined by PCR detection of C. difficile and Toxin B genes in fecal samples, modulates the course of ulcerative colitis (UC). Colonized patients harbor the pathogen at the mucosal surface without overt infection, yet colonization may exacerbate early disease. Methods We applied single-cell RNA sequencing (scRNA-seq) to intestinal biopsies from 24 UC patients and integrated 5 healthy control datasets from the Human Cell Atlas, defining colonization status by PCR/ELISA detection. Results We hypothesized that C. difficile—driven inflammation sustains chronic colonic injury via expansion of a distinct IL1B+ monocyte subset. scRNA-seq revealed this subset uniquely enriched in colonized UC tissue, exhibiting gene programs related to neutrophil recruitment and leukocyte chemotaxis. We further identified a marked expansion of infiltrating inflammatory monocytes along the chemokine axis, accompanied by upregulation of CCL2, CCL3, CXCL3, and CXCL8. Trajectory analysis demonstrated that these monocytes differentiate into macrophages within the tissue, enhancing recruitment in inflamed lesions. Moreover, interactions between CCL2-expressing glial cells and monocytes were implicated in amplifying local inflammation. Conclusion These findings identify C. difficile—induced IL1B+ infiltrating monocytes as key amplifiers of innate immune recruitment and drivers of persistent inflammation in UC, providing mechanistic insights into pathogen-associated disease exacerbation. Funding Source This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. RS-2022-NR067309). Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)
Language: English
Subfield: Genetics
Open Access status: bronze
OpenAlex ID: W7171552072
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