Impaired resistance and enhanced pathology during infection with a noninvasive, attaching-effacing enteric bacterial pathogen, Citrobacter rodentium, in mice lacking IL-12 or IFN-gamma
Mice infected with Citrobacter rodentium represent an excellent model in which to examine immune defenses against an attaching-effacing enteric bacterial pathogen. Colonic tissue from mice infected with C. rodentium harbors increased transcripts for IL-12 and IFN-γ and displays mucosal pathology com...
| Main Authors: | , , , |
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| 格式: | Journal article |
| 語言: | English |
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American Association of Immunologists
2002
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| _version_ | 1826268705549451264 |
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| author | Simmons, C Goncalves, N Ghaem-Maghami, M al., E |
| author_facet | Simmons, C Goncalves, N Ghaem-Maghami, M al., E |
| author_sort | Simmons, C |
| collection | OXFORD |
| description | Mice infected with Citrobacter rodentium represent an excellent model in which to examine immune defenses against an attaching-effacing enteric bacterial pathogen. Colonic tissue from mice infected with C. rodentium harbors increased transcripts for IL-12 and IFN-γ and displays mucosal pathology compared with uninfected controls. In this study, the role of IL-12 and IFN-γ in host defense and mucosal injury during C. rodentium infection was examined using gene knockout mice. IL-12p40−/− and IFN-γ−/− mice were significantly more susceptible to mucosal and gut-derived systemic C. rodentium infection. In particular, a proportion of IL-12p40−/− mice died during infection. Analysis of the gut mucosa of IL-12p40−/− mice revealed an influx of CD4+ T cells and a local IFN-γ response. Infected IL-12p40−/− and IFN-γ−/− mice also mounted anti-Citrobacter serum and gut-associated IgA responses and strongly expressed inducible NO synthase (iNOS) in mucosal tissue, despite diminished serum nitrite/nitrate levels. However, iNOS does not detectably contribute to host defense against C. rodentium, as iNOS−/− mice were not more susceptible to infection. However, C57BL/6 mice infected with C. rodentium up-regulated expression of the mouse β-defensin (mBD)-1 and mBD-3 in colonic tissue. In contrast, expression of mBD-3, but not mBD-1, was significantly attenuated during infection of IL-12- and IFN-γ-deficient mice, suggesting mBD-3 may contribute to host defense. These studies are among the first to examine mechanisms of host resistance to an attaching-effacing pathogen and show an important role for IL-12 and IFN-γ in limiting bacterial infection of the colonic epithelium. |
| first_indexed | 2024-03-06T21:13:43Z |
| format | Journal article |
| id | oxford-uuid:3f0e44fb-a5b4-4755-b95f-9cbbf42c7101 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:13:43Z |
| publishDate | 2002 |
| publisher | American Association of Immunologists |
| record_format | dspace |
| spelling | oxford-uuid:3f0e44fb-a5b4-4755-b95f-9cbbf42c71012022-03-26T14:29:38ZImpaired resistance and enhanced pathology during infection with a noninvasive, attaching-effacing enteric bacterial pathogen, Citrobacter rodentium, in mice lacking IL-12 or IFN-gammaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3f0e44fb-a5b4-4755-b95f-9cbbf42c7101EnglishSymplectic Elements at OxfordAmerican Association of Immunologists2002Simmons, CGoncalves, NGhaem-Maghami, Mal., EMice infected with Citrobacter rodentium represent an excellent model in which to examine immune defenses against an attaching-effacing enteric bacterial pathogen. Colonic tissue from mice infected with C. rodentium harbors increased transcripts for IL-12 and IFN-γ and displays mucosal pathology compared with uninfected controls. In this study, the role of IL-12 and IFN-γ in host defense and mucosal injury during C. rodentium infection was examined using gene knockout mice. IL-12p40−/− and IFN-γ−/− mice were significantly more susceptible to mucosal and gut-derived systemic C. rodentium infection. In particular, a proportion of IL-12p40−/− mice died during infection. Analysis of the gut mucosa of IL-12p40−/− mice revealed an influx of CD4+ T cells and a local IFN-γ response. Infected IL-12p40−/− and IFN-γ−/− mice also mounted anti-Citrobacter serum and gut-associated IgA responses and strongly expressed inducible NO synthase (iNOS) in mucosal tissue, despite diminished serum nitrite/nitrate levels. However, iNOS does not detectably contribute to host defense against C. rodentium, as iNOS−/− mice were not more susceptible to infection. However, C57BL/6 mice infected with C. rodentium up-regulated expression of the mouse β-defensin (mBD)-1 and mBD-3 in colonic tissue. In contrast, expression of mBD-3, but not mBD-1, was significantly attenuated during infection of IL-12- and IFN-γ-deficient mice, suggesting mBD-3 may contribute to host defense. These studies are among the first to examine mechanisms of host resistance to an attaching-effacing pathogen and show an important role for IL-12 and IFN-γ in limiting bacterial infection of the colonic epithelium. |
| spellingShingle | Simmons, C Goncalves, N Ghaem-Maghami, M al., E Impaired resistance and enhanced pathology during infection with a noninvasive, attaching-effacing enteric bacterial pathogen, Citrobacter rodentium, in mice lacking IL-12 or IFN-gamma |
| title | Impaired resistance and enhanced pathology during infection with a noninvasive, attaching-effacing enteric bacterial pathogen, Citrobacter rodentium, in mice lacking IL-12 or IFN-gamma |
| title_full | Impaired resistance and enhanced pathology during infection with a noninvasive, attaching-effacing enteric bacterial pathogen, Citrobacter rodentium, in mice lacking IL-12 or IFN-gamma |
| title_fullStr | Impaired resistance and enhanced pathology during infection with a noninvasive, attaching-effacing enteric bacterial pathogen, Citrobacter rodentium, in mice lacking IL-12 or IFN-gamma |
| title_full_unstemmed | Impaired resistance and enhanced pathology during infection with a noninvasive, attaching-effacing enteric bacterial pathogen, Citrobacter rodentium, in mice lacking IL-12 or IFN-gamma |
| title_short | Impaired resistance and enhanced pathology during infection with a noninvasive, attaching-effacing enteric bacterial pathogen, Citrobacter rodentium, in mice lacking IL-12 or IFN-gamma |
| title_sort | impaired resistance and enhanced pathology during infection with a noninvasive attaching effacing enteric bacterial pathogen citrobacter rodentium in mice lacking il 12 or ifn gamma |
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