Role of GM-CSF in the inflammatory cytokine network that regulates neutrophil influx into the colonic mucosa during Clostridium difficile infection in mice
| Autor: | Roderick A. McDonald, Nicole R. Falkowski, Charles R. Frank, Gary B. Huffnagle, Andrew J. McDermott, Vincent B. Young |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Microbiology (medical)
Male Chemokine Colon Neutrophils Clostridium difficile toxin A Cefoperazone Biology Microbiology Article Proinflammatory cytokine medicine Animals Colitis Intestinal Mucosa Clostridioides difficile Gastroenterology Antibodies Monoclonal Granulocyte-Macrophage Colony-Stimulating Factor Clostridium difficile medicine.disease Anti-Bacterial Agents Mice Inbred C57BL Disease Models Animal Infectious Diseases Neutrophil elastase Immunology biology.protein Clostridium Infections CXCL9 Cytokines SLPI |
| Popis: | 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-CS F. We utilized a neutralizing monoclonal antibody (mAb) against GM-CS F in a murine model to study the role of GM-CS F during acute C. difficile colitis. Cefoperazone-treated mice were challenged with C. difficile (strain 630) spores. Expression of GM-CS F was significantly increased in animals challenged with C. difficile. Treatment with an anti-GM-CS F 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-1β, as well as iNOS, was significantly reduced following anti-GM-CS F treatment. Expression of the neutrophil chemokines CXCL1 and CXCL2, but not the chemokines CC L2, CC L4, CXCL9, and CXCL10, was significantly reduced by anti-GM-CS F 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-CS F 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. |
| Databáze: | OpenAIRE |
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