Role of GM-CSF in the inflammatory cytokine network that regulates neutrophil influx into the colonic mucosa during Clostridium difficile infection in mice.
Gut Microbes
; 5(4): 476-84, 2014 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-25045999
ABSTRACT
Clostridium difficile infection in antibiotic-treated mice results in acute colitis characterized by severe intestinal histopathology, robust neutrophil influx, and increased expression of numerous inflammatory cytokines, including GM-CSF. We utilized a neutralizing monoclonal antibody (mAb) against GM-CSF in a murine model to study the role of GM-CSF during acute C. difficile colitis. Cefoperazone-treated mice were challenged with C. difficile (strain 630) spores. Expression of GM-CSF was significantly increased in animals challenged with C. difficile. Treatment with an anti-GM-CSF mAb did not alter C. difficile colonization levels, weight loss, or expression of IL-22 and RegIIIγ. However, expression of the inflammatory cytokines TNFα and IL-1ß, as well as iNOS, was significantly reduced following anti-GM-CSF treatment. Expression of the neutrophil chemokines CXCL1 and CXCL2, but not the chemokines CCL2, CCL4, CXCL9, and CXCL10, was significantly reduced by anti-GM-CSF treatment. Consistent with a decrease in neutrophil-attractant chemokine expression, there were fewer neutrophils in histology sections and a reduction in the expression of secretory leukocyte protease inhibitor (SLPI), a tissue anti-protease that protects against damage by secreted neutrophil elastase. These data indicate that GM-CSF plays a role in the inflammatory signaling network that drives neutrophil recruitment in response to C. difficile infection but does not appear to play a role in clearance of the infection.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Clostridioides difficile
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Citocinas
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Factor Estimulante de Colonias de Granulocitos y Macrófagos
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Infecciones por Clostridium
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Colon
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Mucosa Intestinal
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Neutrófilos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2014
Tipo del documento:
Article