title: Clostridium difficile infection aggravates colitis in interleukin 10-deficient mice.
abstract: OBJECTIVE
  To investigate the effect of Clostridium difficile (C. difficile) infection in an interleukin 10-deficient (IL-10(-/-)) mouse model of inflammatory bowel disease.
  
  
  METHODS
  Bone marrow-derived dendritic cells isolated from wild type (WT) and IL-10(-/-)mice were stimulated for 4 h with C. difficile toxin A (200 μg/mL), and gene expression of interferon (IFN)-γ, IL-12 and IL-23 was determined by real-time reverse transcription polymerase chain reaction. WT and IL-10(-/-) mice (n = 20 each) were exposed to an antibiotic cocktail for three days and then were injected with clindamycin (i.p.). Mice (n = 10 WT, 10 IL-10(-/-)) were then challenged with oral administration of C. difficile (1 × 10(5) colony forming units of strain VPI 10463). Animals were monitored daily for 7 d for signs of colitis. Colonic tissue samples were evaluated for cytokine gene expression and histopathologic analysis.
  
  
  RESULTS
  C. difficile toxin A treatment induced IFN-γ gene expression to a level that was significantly higher in BDMCs from IL-10(-/-) compared to those from WT mice (P < 0.05). However, expression of IL-12 and IL-23 was not different among the groups. Following C. difficile administration, mice developed diarrhea and lost weight within 2-3 d. Weight loss was significantly greater in IL-10(-/-) compared to WT mice (P < 0.05). C. difficile infection induced histopathologic features typical of colitis in both IL-10(-/-) and WT mice. The histopathologic severity score was significantly higher in the IL-10(-/-) than in WT mice (mean ± standard error; 5.50 ± 0.53 vs 2.44 ± 0.46; P < 0.05). This was accompanied by a significantly greater increase in IFN-γ gene expression in colonic tissues from IL-10(-/-) than from WT mice challenged with C. difficile (P < 0.05).
  
  
  CONCLUSIONS
  These results indicate that colitis is more severe after C. difficile infection in IL-10(-/-)mice, and that IFN-γ expression is involved in this process.
authors.affiliation: Mi Na Kim, Seoul National University Healthcare System Gangnam Center, Seoul National University Hospital, Seoul 135-984, South Korea.
authors.forename: Mi Na
authors.initials: MN
authors.lastname: Kim
authors.affiliation: Mi Na Kim, Seoul National University Healthcare System Gangnam Center, Seoul National University Hospital, Seoul 135-984, South Korea.
authors.forename: Seong-Joon
authors.initials: SJ
authors.lastname: Koh
authors.affiliation: Mi Na Kim, Seoul National University Healthcare System Gangnam Center, Seoul National University Hospital, Seoul 135-984, South Korea.
authors.forename: Jung Mogg
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Mi Na Kim, Seoul National University Healthcare System Gangnam Center, Seoul National University Hospital, Seoul 135-984, South Korea.
authors.forename: Jong Pil
authors.initials: JP
authors.lastname: Im
authors.affiliation: Mi Na Kim, Seoul National University Healthcare System Gangnam Center, Seoul National University Hospital, Seoul 135-984, South Korea.
authors.forename: Hyun Chae
authors.initials: HC
authors.lastname: Jung
authors.affiliation: Mi Na Kim, Seoul National University Healthcare System Gangnam Center, Seoul National University Hospital, Seoul 135-984, South Korea.
authors.forename: Joo Sung
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016360:Clostridioides difficile / Q000472:pathogenicity*; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D004768:Enterotoxins / Q000494:pharmacology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors; D015431:Weight Loss
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; C556062:IL10 protein, mouse; D053759:Interleukin-23; D012333:RNA, Messenger; C041348:tcdA protein, Clostridium difficile; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: Clostridium difficile; Colitis; Inflammatory bowel disease; Interferon-γ; Interleukin 10-deficient mice