| 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
|
| リソース情報 |
| 実験動物マウス |
RBRC00858
RBRC01420 |
