A164 SINGLE-CELL RNASEQ INDICATES INCREASE IN COLONIC REGULATORY MACROPHAGES DURING <i>CITROBACTER RODENTIUM</i> INFECTIOUS COLITIS
Why this work is in the frame
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Bibliographic record
Abstract
Abstract Background Citrobacter rodentium (CR) is a murine attaching and effacing enteric bacterial pathogen that induces colitis and mimics enteropathogenic and enterohemorrhagic E. coli in humans. Studies of macrophages during CR infection have focused on proinflammatory functions, paying less attention to M2 or regulatory macrophages. We have shown that IL-4-treated macrophages (M(IL4)) have promising potential as a novel anti-colitic therapy using chemical-induced colitis in mice. However, any benefit of M(IL4)s in infectious colitis is unknown. This study tests the hypothesis that regulatory macrophages, specifically M(IL4)s, limit the severity of CR-infectious colitis. Aims i. Determine if M2 macrophages increase in the colon of CR infected mice. ii. Assess the impact of M(IL4) treatment in CR infection severity and inflammation. Methods C57Bl/6 mice were orally infected with CR (5x108 CFU), and colons were collected during the colonization, expansion, and clearance phases (0, 3, 8, 21 days post-infection, DPI) for single-cell RNAseq to examine immune profiles and differentially expressed genes (DEG). The effect of M(IL4) treatment was assessed through ip. delivery of M(IL4)s (106cells) two days before CR infection followed by analysis of bacterial shedding and colonic histopathology. Inflammation was measured by neutrophil-mediated lipocalin-2 in feces by ELISA and RT-qPCR for mRNA expression of the anti-microbial peptide, REGIIIγ, and Th1 cytokine, IFN-γ. Results Peaking at 3 DPI, there was a significant increase in arginase1+ Relma+ Ym1+ M2 macrophages in the colon of CR-infected mice compared to proinflammatory M1 subsets. These M2-type cells showed upregulated expression of Cxcl9 and Acod1 mRNA, which possess antimicrobial activity essential in mitigating CR infection. Pretreatment with M(IL4)s did not exacerbate CR infection as bacterial shedding and histopathology scores (n=13) were similar in both groups, with all mice clearing CR by 18 DPI (n=5). Infection with CR was accompanied by increased fecal lipocalin and tissue REGIIIγ and IFNγ mRNA, independent of M(IL4) treatment (n=13). Conclusions This study suggests a formerly unappreciated antimicrobial role of M2 macrophages in the defense against CR. While M(IL4) treatment did not improve the outcome of infection with CR, neither did it exaggerate the severity of the infection, suggesting that the adoption of M(IL4) therapy for IBD would not increase the individual’s susceptibility to enteric infection. Funding Agencies NRC
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it