Silencing SOCS1 via Liposome-Packed siRNA Sustains TLR4-Ligand Adjuvant
Infectious diseases remain one of the leading causes of death worldwide. Vaccination is a powerful instrument to avert a variety of those by inducing a pathogen-specific immune response and ensure a long-lasting protection against the respective infection. Nevertheless, due to increasing numbers of...
Gespeichert in:
| Hauptverfasser: | , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
04 June 2019
|
| In: |
Frontiers in immunology
Year: 2019, Jahrgang: 10 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2019.01279 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fimmu.2019.01279 Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2019.01279/full 
|
| Verfasserangaben: | Dagmar Hildebrand, Camila Metz-Zumaran, Greta Jaschkowitz and Klaus Heeg |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1671529731 | ||
| 003 | DE-627 | ||
| 005 | 20210816192857.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 190816s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fimmu.2019.01279 |2 doi | |
| 035 | |a (DE-627)1671529731 | ||
| 035 | |a (DE-599)KXP1671529731 | ||
| 035 | |a (OCoLC)1264090311 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Hildebrand, Dagmar |d 1979- |e VerfasserIn |0 (DE-588)1013137892 |0 (DE-627)704967073 |0 (DE-576)346073596 |4 aut | |
| 245 | 1 | 0 | |a Silencing SOCS1 via Liposome-Packed siRNA Sustains TLR4-Ligand Adjuvant |c Dagmar Hildebrand, Camila Metz-Zumaran, Greta Jaschkowitz and Klaus Heeg |
| 264 | 1 | |c 04 June 2019 | |
| 300 | |a 12 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 16.08.2019 | ||
| 520 | |a Infectious diseases remain one of the leading causes of death worldwide. Vaccination is a powerful instrument to avert a variety of those by inducing a pathogen-specific immune response and ensure a long-lasting protection against the respective infection. Nevertheless, due to increasing numbers of immunocompromised patients and emergence of more aggressive pathogens existing vaccination techniques are limited. In our study we investigated a new strategy to strengthen vaccine adjuvant in order to increase immunity against infectious diseases. The strategy is based on an amplification of Toll like receptor 4 (TLR4) -induced activation of antigen-presenting cells (APCs) by turning off a powerful endogenous inhibitor of APC-activation. TLR4 signaling induces the release of cytokines that bind autocrine and paracrine to receptors, activating the Janus kinase (JAK) 2/ signal transducers and activators of transcription (STAT) 3 cascade. Subsequently, STAT3 induces expression of suppressor of cytokine signaling (SOCS) 1 that terminates the inflammatory response. In the approach, TLR4-adjuvant monophosphoryl lipid A (MPLA)-stimulated monocyte-activation is reinforced and sustained by silencing SOCS1 via lipid nanoparticle-enclosed siRNA (L-siRNA). L-siRNA is transported into primary cells without any toxic side effects and protected from early degradation. Through lipid core-embedded functional groups the lipid particle escapes from endosomes and releases the siRNA when translocated into the cytoplasm. SOCS1is potently silenced, and SOCS1-mediated termination of NFκB signaling is abrogated. Consequently, the MPLA -stimulated activation of APCs, monitored by release of pro-inflammatory cytokines such as IL-6, TNFα and IL-1β, upregulation of MHC class II molecules and costimulatory CD80/CD86 is strongly enhanced and prolonged. SOCS1-silenced APCs, pulsed with liposomal tetanus light chain toxin (TeTxLC) antigen, activate autologous T cells much more intensive than SOCS1-expressing cells. Importantly, expansion of cocultured CD4+ as well as CD8+ T cells is remarkably enhanced. Furthermore, our results point towards a broad T helper cell response as TH1 typical as well as TH2 characteristic cytokines are elevated. Taken together, this study in the human system comprises a translational potential to develop more effective vaccines against infectious diseases by inhibition of the endogenous negative-feedback loop in APCs. | ||
| 700 | 1 | |a Heeg, Klaus |d 1956- |e VerfasserIn |0 (DE-588)133238369 |0 (DE-627)539308587 |0 (DE-576)299716805 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in immunology |d Lausanne : Frontiers Media, 2010 |g 10(2019) Artikel-Nummer 1279, 12 Seiten |h Online-Ressource |w (DE-627)657998354 |w (DE-600)2606827-8 |w (DE-576)343624834 |x 1664-3224 |7 nnas |a Silencing SOCS1 via Liposome-Packed siRNA Sustains TLR4-Ligand Adjuvant |
| 773 | 1 | 8 | |g volume:10 |g year:2019 |g extent:12 |a Silencing SOCS1 via Liposome-Packed siRNA Sustains TLR4-Ligand Adjuvant |
| 856 | 4 | 0 | |u https://doi.org/10.3389/fimmu.2019.01279 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.frontiersin.org/articles/10.3389/fimmu.2019.01279/full |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20190816 | ||
| 993 | |a Article | ||
| 994 | |a 2019 | ||
| 998 | |g 133238369 |a Heeg, Klaus |m 133238369:Heeg, Klaus |d 910000 |d 911700 |e 910000PH133238369 |e 911700PH133238369 |k 0/910000/ |k 1/910000/911700/ |p 4 |y j | ||
| 998 | |g 1013137892 |a Hildebrand, Dagmar |m 1013137892:Hildebrand, Dagmar |d 910000 |d 911700 |e 910000PH1013137892 |e 911700PH1013137892 |k 0/910000/ |k 1/910000/911700/ |p 1 |x j | ||
| 999 | |a KXP-PPN1671529731 |e 3507385724 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"id":{"doi":["10.3389/fimmu.2019.01279"],"eki":["1671529731"]},"recId":"1671529731","origin":[{"dateIssuedKey":"2019","dateIssuedDisp":"04 June 2019"}],"relHost":[{"type":{"bibl":"periodical","media":"Online-Ressource"},"recId":"657998354","disp":"Silencing SOCS1 via Liposome-Packed siRNA Sustains TLR4-Ligand AdjuvantFrontiers in immunology","part":{"volume":"10","text":"10(2019) Artikel-Nummer 1279, 12 Seiten","year":"2019","extent":"12"},"pubHistory":["1.2010 -"],"origin":[{"dateIssuedDisp":"2010-","dateIssuedKey":"2010","publisherPlace":"Lausanne","publisher":"Frontiers Media"}],"id":{"zdb":["2606827-8"],"eki":["657998354"],"issn":["1664-3224"]},"note":["Gesehen am 07.11.13"],"language":["eng"],"title":[{"title":"Frontiers in immunology","title_sort":"Frontiers in immunology"}],"physDesc":[{"extent":"Online-Ressource"}]}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"person":[{"display":"Hildebrand, Dagmar","family":"Hildebrand","role":"aut","given":"Dagmar"},{"family":"Heeg","display":"Heeg, Klaus","role":"aut","given":"Klaus"}],"name":{"displayForm":["Dagmar Hildebrand, Camila Metz-Zumaran, Greta Jaschkowitz and Klaus Heeg"]},"note":["Gesehen am 16.08.2019"],"language":["eng"],"title":[{"title_sort":"Silencing SOCS1 via Liposome-Packed siRNA Sustains TLR4-Ligand Adjuvant","title":"Silencing SOCS1 via Liposome-Packed siRNA Sustains TLR4-Ligand Adjuvant"}],"physDesc":[{"extent":"12 S."}]} | ||
| SRT | |a HILDEBRANDSILENCINGS0420 | ||