Interferon regulatory factor 7‐mediated responses are defective in cord blood plasmacytoid dendritic cells

Danis, Bénédicte; George, Thaddeus C.; Goriely, Stanislas; Dutta, Binita; Renneson, Joelle; Gatto, Laurent; Fitzgerald-Bocarsly, Patricia; Marchant, Arnaud; Goldman, Michel; Willems, Fabienne; Wit, Dominique De

doi:10.1002/eji.200737760

Cited by 88 publications

(85 citation statements)

References 36 publications

(42 reference statements)

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“…The more severe manifestations seen in IRF3/7 Ϫ/Ϫ (and IFNAR Ϫ/Ϫ ) mice, hemorrhage, thrombocytopenia, and hypovolemic shock, have also been reported for severe CHIKV infections in human neonates and children (16,47), with such manifestations occasionally associated with mortality in neonates (16,37,45,47,57). Human neonates have defective innate antiviral responses, including defective IRF7-mediated responses (12,31). Hemorrhagic fever associated with CHIKV infections in children (13,24,45) and some adults (39,47) has also been reported.…”

Section: Discussionmentioning

confidence: 88%

“…Increased mortality was also seen after infection of IRF7 Ϫ/Ϫ or IRF3 Ϫ/Ϫ mice with the virulent West Nile virus strain (NY99), whereas infection with the naturally attenuated West Nile strain (Kunjin) was universally lethal only in IRF3/7 Ϫ/Ϫ doubleknockout mice (9). IRF7 has been shown to be important for optimum production of IFN-␣/␤ in murine embryonic fibroblasts (MEFs) after infection with a number of viruses (22) and is critical for IFN-␣/␤ production by plasmacytoid dendritic cells (12). IRF3 has been shown to be important for optimum IFN-␣/␤ production by nonhematopoietic and hematopoietic cells in response to certain virus infections (22), and IRF3-dependent apoptotic signaling can also contribute significantly to the host's protection from viral infection (4).…”

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confidence: 99%

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Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock

Rudd

Wilson

Gardner

et al. 2012

J Virol

166

244

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f Chikungunya virus (CHIKV) infections can produce severe disease and mortality. Here we show that CHIKV infection of adult mice deficient in interferon response factors 3 and 7 (IRF3/7 ؊/؊ ) is lethal. Mortality was associated with undetectable levels of alpha/beta interferon (IFN-␣/␤) in serum, ϳ50-and ϳ10-fold increases in levels of IFN-␥ and tumor necrosis factor (TNF), respectively, increased virus replication, edema, vasculitis, hemorrhage, fever followed by hypothermia, oliguria, thrombocytopenia, and raised hematocrits. These features are consistent with hemorrhagic shock and were also evident in infected IFN-␣/␤ receptor-deficient mice. In situ hybridization suggested CHIKV infection of endothelium, fibroblasts, skeletal muscle, mononuclear cells, chondrocytes, and keratinocytes in IRF3/7 ؊/؊ mice; all but the latter two stained positive in wild-type mice. Vaccination protected IRF3/7 ؊/؊ mice, suggesting that defective antibody responses were not responsible for mortality. IPS-1-and TRIF-dependent pathways were primarily responsible for IFN-␣/␤ induction, with IRF7 being upregulated >100-fold in infected wild-type mice. These studies suggest that inadequate IFN-␣/␤ responses following virus infection can be sufficient to induce hemorrhagic fever and shock, a finding with implications for understanding severe CHIKV disease and dengue hemorrhagic fever/dengue shock syndrome.

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Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 99%

Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock

Rudd

Wilson

Gardner

et al. 2012

J Virol

166

244

View full text Add to dashboard Cite

show abstract

“…It is well established that after antigen stimulation, both myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) from human cord blood express lower levels of MHC class II and the costimulatory molecules CD80 and CD86 than do adult peripheral blood DCs (31)(32)(33). Furthermore, neonatal mDCs and pDCs have a limited ability to produce IFN-α/β after pattern recognition receptor stimulation (34,35). In mammals, antigen presentation by these immature DCs results in the development of anergy or tolerance by the responding lymphocytes.…”

Section: Vaccinementioning

confidence: 99%

Puzzling inefficiency of H5N1 influenza vaccines in Egyptian poultry

Kim

Kayali

Walker

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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In Egypt, efforts to control highly pathogenic H5N1 avian influenza virus in poultry and in humans have failed despite increased biosecurity, quarantine, and vaccination at poultry farms. The ongoing circulation of HP H5N1 avian influenza in Egypt has caused >100 human infections and remains an unresolved threat to veterinary and public health. Here, we describe that the failure of commercially available H5 poultry vaccines in Egypt may be caused in part by the passive transfer of maternal H5N1 antibodies to chicks, inhibiting their immune response to vaccination. We propose that the induction of a protective immune response to H5N1 is suppressed for an extended period in young chickens. This issue, among others, must be resolved and additional steps must be taken before the outbreaks in Egypt can be controlled.

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“…responses are known to be defective/underdeveloped (Levy 2007, Danis, George et al 2008 (Lee, Liu et al 2006, Pang, Cardosa et al 2007). …”

Section: Chikv Infection Of Ifnar -/-Mice Results In Rapid Lethal Hymentioning

confidence: 99%

“…The observed difference in mutation accrual may have implications chronic disease, whereby less mutated viral RNA is able to persist long term in the feet, while heavily mutated viral RNA in the lymph nodes accumulates too many mutations, and is thus unable to persist. (Levy 2007, Danis, George et al 2008, are more prone to development of DHF/DSS (Guzmán, Kouri et al 2002), and a study of children and young adults, found IRF7 transcriptional activity was associated with protection against development of DHS/DSS (Hoang, Lynn et al 2010). Furthermore, DHS/DSS patients have been found to have reduced type I IFN transcript levels (Simmons, Popper et al 2007).…”

Section: Summary Of Major Findingsmentioning

confidence: 99%

The role of type I interferon in the immunobiology of chikungunya virus

Wilson¹

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Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that can cause explosive outbreaks of a febrile, arthritic/arthralgic disease usually lasting weeks to months, and in rare cases, more than a year. In 2004, the largest ever CHIKV outbreak began in Kenya, spreading to islands of the Indian Ocean, India, South East Asia and major outbreaks have recently occurred in the South Pacific Islands and the Caribbean.The host type I interferon (IFN) response is crucial for effective control of CHIKV infection.Herein, the dynamics, source and responses generated by the type I IFNs following CHIKV infection were investigated. RNASeq was undertaken to examine, in detail, the nature of the type I IFN responses generated in the feet and inguinal lymph nodes of mice following CHIKV infection at days 2 and 7 post-infection. High quality sequencing data was generated from III host and viral poly-adenylated RNA, permitting investigation of low level gene transcription from both sources, and the identification of novel genes/transcripts, in addition to analysis of differential gene expression.Investigation of host transcriptional activity revealed a type I IFN dominated immune response, in spite of a low induction of type I IFN mRNA transcripts at day 2 and an absence of type I IFN mRNA induction on day 7. Many type I IFN-regulated genes, including IRF7, remained up-regulated in the feet at day 7, suggesting type I IFNindependent mechanisms for maintenance of type I IFN-regulated gene expression. Six novel IRF3 isoforms and a potentially novel protein coding gene were also identified.RNA-Seq analysis of CHIKV transcriptional activity reflected the known CHIKV replication kinetics, in which virus replicates in the joints, and spreads to the draining lymph nodes, with viral titres peaking at day 2 and largely resolving at day 7. Assessment of mutations within the CHIKV genome showed an accumulation with time, with error accumulation higher in the lymph nodes than in the feet. These studies represent the first deep sequencing analysis of CHIKV genomes in tissues.The findings in this thesis substantially add to our knowledge of the role and function of the immune response after CHIKV, illustrating for the first time that type I IFNs protect against haemorrhagic shock and that expression of type I IFN inducible genes is maintained well after type I IFN induction has waned.

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Interferon regulatory factor 7‐mediated responses are defective in cord blood plasmacytoid dendritic cells

Cited by 88 publications

References 36 publications

Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock

Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock

Puzzling inefficiency of H5N1 influenza vaccines in Egyptian poultry

The role of type I interferon in the immunobiology of chikungunya virus

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