論文 - 詳細
| RRC ID | 12360 |
|---|---|
| 著者 | Prantner D, Sikes JD, Hennings L, Savenka AV, Basnakian AG, Nagarajan UM. |
| タイトル | Interferon regulatory transcription factor 3 protects mice from uterine horn pathology during Chlamydia muridarum genital infection. |
| ジャーナル | Infect Immun |
| Abstract |
Mice with the type I interferon (IFN) receptor gene knocked out (IFNAR KO mice) or deficient for alpha/beta IFN (IFN-α/β) signaling clear chlamydial infection earlier than control mice and develop less oviduct pathology. Initiation of host IFN-β transcription during an in vitro chlamydial infection requires interferon regulatory transcription factor 3 (IRF3). The goal of the present study was to characterize the influence of IRF3 on chlamydial genital infection and its relationship to IFN-β expression in the mouse model. IRF3 KO mice were able to resolve infection as well as control mice, overcoming increased chlamydial colonization and tissue burden early during infection. As previously observed for IFNAR KO mice, IRF3 KO mice generated a potent antigen-specific T cell response. However, in contrast to IFNAR KO mice, IRF3 KO mice exhibited unusually severe dilatation and pathology in the uterine horns but normal oviduct pathology after infection. Although IFN-β expression in vivo was dependent on the presence of IRF3 early in infection (before day 4), the IFN-independent function of IRF3 was likely driving this phenotype. Specifically, early during infection, the number of apoptotic cells and the number of inflammatory cells were significantly less in uterine horns from IRF3 KO mice than in those from control mice, despite an increased chlamydial burden. To delineate the effects of IFN-β versus IRF3, neutralizing IFN-β antibody was administered to wild-type (WT) mice during chlamydial infection. IFN-β depletion in WT mice mimicked that in IFNΑR KO mice but not that in IRF3 KO mice with respect to both chlamydial clearance and reduced oviduct pathology. These data suggest that IRF3 has a role in protection from uterine horn pathology that is independent of its function in IFN-β expression. |
| 巻・号 | 79(10) |
| ページ | 3922-33 |
| 公開日 | 2011-10-1 |
| DOI | 10.1128/IAI.00140-11 |
| PII | IAI.00140-11 |
| PMID | 21788382 |
| PMC | PMC3187243 |
| MeSH | Animals Chlamydia Infections / immunology* Chlamydia Infections / microbiology Chlamydia muridarum / immunology* Chlamydia muridarum / pathogenicity Cytokines / metabolism Disease Models, Animal Female Genital Diseases, Female / immunology* Genital Diseases, Female / microbiology Interferon Regulatory Factor-3 / genetics Interferon Regulatory Factor-3 / immunology* Interferon Regulatory Factor-3 / metabolism Interferon-beta / genetics Interferon-beta / metabolism Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Knockout Signal Transduction T-Lymphocytes / immunology Uterus / microbiology Uterus / pathology* |
| IF | 3.201 |
| 引用数 | 20 |
| WOS 分野 | INFECTIOUS DISEASES IMMUNOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Policy sources |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC00858 RBRC01420 |