AG Kathrin Sutter

Nachwuchsgruppe TRR60

“Interferon-alpha Subtypen in chronischen Virusinfektionen”
“Interferon-alpha Subtypes in chronic viral infections”

Forschungsschwerpunkte

  • Interferon-alpha Subtypen
  • Modulation von Immunzellen
  • Immuntherapien
  • NK-Zellen 

Projekt

Während den meisten Virusinfektionen ist die erste Immunantwort charakterisiert durch die Induktion von Typ I Interferon (IFN). IFN gehört zu einer Genfamilie, welche bis zu 13 verschiedene IFN-α Subtypen und IFN-β mit einschließt. Diese Interferone weisen alle unterschiedliche biologische Aktivitäten auf wie z.B. antivirale, anti-proliferative und immunmodulatorische Eigenschaften. Nach ihrer Induktion, binden alle Interferone an den gleichen Rezeptor, was zu der Expression zahlreicher verschiedener IFN-stimulierter Gene führt, welche für antivirale Proteine kodieren, die direkt die virale Replikation inhibieren wie auch die Funktion von Immunzellen modulieren. Daher ist die Induktion von Typ I IFN ein wirkungsvolles Mittel gegen Virusinfektionen anzukämpfen. Viele Viren haben Wege gefunden der IFN-Antwort zu entgehen. Deshalb sollte die therapeutische Gabe von exogenem Typ I IFN ein großes Potential für zukünftige Immuntherapien gegen Virusinfektionen besitzen. Die Nachwuchsgruppe ist hauptsächlich interessiert an den verschiedenen antiviralen und immunmodulatorischen Eigenschaften aller humanen und murinen IFN-α Subtypen in akuten und chronischen Virusinfektionen. Ein besonderer Augenmerk liegt auf der Induktion der verschiedenen Subtypen, deren Regulation und ihren erschiedenen biologischen Eigenschaften besonders die Modulation von Immunantworten. 

During most viral infections, the immediate host response is characterized by an induction of type I Interferon (IFN). IFN belongs to a multigene family that includes up to 13 different IFN-α subtypes and IFN-β, which have various biological activities, including anti-viral, anti-proliferative and immunomodulatory effects. After induction, they all bind to the same receptor, which results in the expression of numerous different IFN-stimulated genes which encode anti-viral proteins that directly inhibit viral replication as well as modulate immune function. Thus, the induction of type I IFN is a very powerful tool for the host to fight virus infections. Many viruses evade this response by various strategies. Therefore, the therapeutic application of exogenous type I IFN should be of great potential for future immunotherapies against viral infections. The junior research group is mainly focusing on the various antiviral and immunomodulatory activities of the different human and murine IFN-α subtypes in acute and chronic viral infections. We are interested in the induction of the subtypes, their regulation and their different biological activities especially the modulation of immune responses.

Arbeitsgruppe

group leader

Dr. rer nat. Kathrin Sutter (geb. Gibbert)
Kathrin.sutter@uni-due.de
0201-723-83250

 

(PhD student)

M.Sc. Julia Dickow
Julia.dickow@uni-due.de
0201-723-4343

M.Sc. Julia Ickler
Julia.ickler@uni-due.de
Tel.: 0201-723-4343

M.Sc. Rouven-Luca Kaiserling
Rouven-luca.kaiserling@uni-due.de
0201-723-4343

(MTA)

Sandra Francois
Sandra.francois@uk-essen.de
0201-723-83737

(research student)

B. Sc. Freya Kretzmer

Ausgewählte Publikationen

2017

Schreiber T, Quinting T, Dittmer U, Fandrey J*, Sutter K*. 2017. Hypoxia-inducible factor-1α is Essential for Macrophage-mediated Erythroblast Proliferation in Acute Friend Retrovirus Infection. Sci Rep accepted (* equally contributed)

Song J, Li S, Zhou Y, Liu J, Francois S, Lu M, Yang D, Dittmer U, Sutter K. 2017. Different antiviral effects of IFNalpha subtypes in a mouse model of HBV infection. Sci Rep 7:334.

Zhou Y, Li S, Tang Z, Xu C, Huang S, Wu J, Dittmer U, Dickow J, Sutter K, Lu M, Yang D, Song J. 2017. Different antiviral effects of IFNalpha and IFNbeta in an HBV mouse model. Immunobiology 222:562-570.

Malyshkina A, Littwitz-Salomon E, Sutter K, Zelinskyy G, Windmann S, Schimmer S, Paschen A, Streeck H, Hasenkrug KJ, Dittmer U. 2017. Fas Ligand-mediated cytotoxicity of CD4+ T cells during chronic retrovirus infection. Sci Rep 7(1):7785.

2016

Littwitz-Salomon E, Dittmer U, Sutter K. 2016. Insufficient natural killer cell responses against retroviruses: how to improve NK cell killing of retrovirus-infected cells. Retrovirology 13:77.

SM Ziegler, Beisel C, Sutter K, Griesbeck M, Hildebrandt H, S HH, Dittmer U, Altfeld M. 2016. Human pDCs display sex-specific differences in type I interferon subtypes

Lavender KJ*, Gibbert K*, Peterson KE, Van Dis E, Francois S, Woods T, Messer RJ, Gawanbacht A, Muller JA, Munch J, Phillips K, Race B, Harper MS, Guo K, Lee EJ, Trilling M, Hengel H, Piehler J, Verheyen J, Wilson CC, Santiago ML, Hasenkrug KJ, Dittmer U. 2016. Interferon Alpha Subtype-Specific Suppression of HIV-1 Infection In Vivo. J Virol 90:6001-6013. (* equally contributed)

 

Bloemker D, Mollerus S, Gibbert K, Dittmer U, Del Rey A, Schedlowski M, Engler H. 2016. Inhibition of catecholamine degradation ameliorates while chemical sympathectomy aggravates the severity of acute Friend retrovirus infection in mice. Brain, behavior, and immunity doi:10.1016/j.bbi.2016.02.011.

Li SX, Barrett BS, Guo K, Kassiotis G, Hasenkrug KJ, Dittmer U, Gibbert K, Santiago ML. 2016. Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection. Scientific reports 6:20425.

Real CI, Lu M, Liu J, Huang X, Trippler M, Hossbach M, Deckert J, Jahn-Hofmann K, Ickenstein LM, John MJ, Gibbert K, Dittmer U, Vornlocher HP, Schirmbeck R, Gerken G, Schlaak JF, Broering R. 2016. Hepatitis B virus genome replication triggers toll-like receptor 3-dependent interferon responses in the absence of hepatitis B surface antigen. Scientific reports 6:24865.

2015

Littwitz-Salomon E, Akhmetzyanova I, Vallet C, Francois S, Dittmer U, Gibbert K. 2015. Activated regulatory T cells suppress effector NK cell responses by an IL-2-mediated mechanism during an acute retroviral infection. Retrovirology 12:66.

Akhmetzyanova I, Drabczyk M, Neff CP, Gibbert K, Dietze KK, Werner T, Liu J, Chen L, Lang KS, Palmer BE, Dittmer U, Zelinskyy G. 2015. PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing. PLoS pathogens 11:e1005224.

Akhmetzyanova I, Drabczyk M, Neff CP, Gibbert K, Dietze KK, Werner T, Liu J, Chen L, Lang KS, Palmer BE, Dittmer U, Zelinskyy G. 2015. Correction: PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing. PLoS pathogens 11:e1005364.

Harper MS, Guo K, Gibbert K, Lee EJ, Dillon SM, Barrett BS, McCarter MD, Hasenkrug KJ, Dittmer U, Wilson CC, Santiago ML. 2015. Interferon-alpha Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms. PLoS pathogens 11:e1005254.

Wu W, Dietze KK, Gibbert K, Lang KS, Trilling M, Yan H, Wu J, Yang D, Lu M, Roggendorf M, Dittmer U, Liu J. 2015. TLR ligand induced IL-6 counter-regulates the anti-viral CD8(+) T cell response during an acute retrovirus infection. Scientific reports 5:10501.

2014

Gibbert K, Francois S, Sigmund AM, Harper MS, Barrett BS, Kirchning CJ, Lu M, Santiago ML, Dittmer U. 2014. Friend retrovirus drives cytotoxic effectors through Toll-like receptor 3. Retrovirology 11:1.

Xu HC, Grusdat M, Pandyra AA, Polz R, Huang J, Sharma P, Deenen R, Kohrer K, Rahbar R, Diefenbach A, Gibbert K, Lohning M, Hocker L, Waibler Z, Haussinger D, Mak TW, Ohashi PS, Lang KS, Lang PA. 2014. Type I interferon protects antiviral CD8+ T cells from NK cell cytotoxicity. Immunity 40:949-960.

Song J, Zhou Y, Li S, Wang B, Zheng X, Wu J, Gibbert K, Dittmer U, Lu M, Yang D. 2014. Susceptibility of different hepatitis B virus isolates to interferon-alpha in a mouse model based on hydrodynamic injection. PloS one 9:e90977.

Broering R, Real CI, John MJ, Jahn-Hofmann K, Ickenstein LM, Kleinehr K, Paul A, Gibbert K, Dittmer U, Gerken G, Schlaak JF. 2014. Chemical modifications on siRNAs avoid Toll-like-receptor-mediated activation of the hepatic immune system in vivo and in vitro. International immunology 26:35-46.

2013

Littwitz E, Francois S, Dittmer U, Gibbert K. 2013. Distinct roles of NK cells in viral immunity during different phases of acute Friend retrovirus infection. Retrovirology 10:127.

Gibbert K, Schlaak J, Yang D, Dittmer U. 2013. IFN-alpha subtypes: distinct biological activities in anti-viral therapy. British journal of pharmacology 168:1048-1058.

Francois S, Peng J, Schwarz T, Duppach J, Gibbert K, Dittmer U, Kraft AR. 2013. NK cells improve control of friend virus infection in mice persistently infected with murine cytomegalovirus. Retrovirology 10:58.

Wobben R, Husecken Y, Lodewick C, Gibbert K, Fandrey J, Winning S. 2013. Role of hypoxia inducible factor-1alpha for interferon synthesis in mouse dendritic cells. Biological chemistry 394:495-505.

Harper MS, Barrett BS, Smith DS, Li SX, Gibbert K, Dittmer U, Hasenkrug KJ, Santiago ML. 2013. IFN-alpha treatment inhibits acute Friend retrovirus replication primarily through the antiviral effector molecule Apobec3. Journal of immunology 190:1583-1590.

Behrendt R, Schumann T, Gerbaulet A, Nguyen LA, Schubert N, Alexopoulou D, Berka U, Lienenklaus S, Peschke K, Gibbert K, Wittmann S, Lindemann D, Weiss S, Dahl A, Naumann R, Dittmer U, Kim B, Mueller W, Gramberg T, Roers A. 2013. Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response. Cell reports doi:10.1016/j.celrep.2013.07.037.

2012

Gibbert K, Joedicke JJ, Meryk A, Trilling M, Francois S, Duppach J, Kraft A, Lang KS, Dittmer U. 2012. Interferon-alpha Subtype 11 Activates NK Cells and Enables Control of Retroviral Infection. PLoS pathogens 8:e1002868.

2011

Gibbert K, Dittmer U. 2011. Distinct antiviral activities of IFN-alpha subtypes. Immunotherapy 3:813-816.

Dietze KK, Zelinskyy G, Gibbert K, Schimmer S, Francois S, Myers L, Sparwasser T, Hasenkrug KJ, Dittmer U. 2011. Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8+ T cells and reduces chronic retroviral set points. Proceedings of the National Academy of Sciences of the United States of America 108:2420-2425.

Zelinskyy G, Myers L, Dietze KK, Gibbert K, Roggendorf M, Liu J, Lu M, Kraft AR, Teichgraber V, Hasenkrug KJ, Dittmer U. 2011. Virus-specific CD8+ T cells upregulate programmed death-1 expression during acute friend retrovirus infection but are highly cytotoxic and control virus replication. Journal of immunology 187:3730-3737.

2010

Gibbert K, Dietze KK, Zelinskyy G, Lang KS, Barchet W, Kirschning CJ, Dittmer U. 2010. Polyinosinic-polycytidylic acid treatment of Friend retrovirus-infected mice improves functional properties of virus-specific T cells and prevents virus-induced disease. Journal of immunology 185:6179-6189.

Sender LY, Gibbert K, Suezer Y, Radeke HH, Kalinke U, Waibler Z. 2010. CD40 ligand-triggered human dendritic cells mount interleukin-23 responses that are further enhanced by danger signals. Molecular immunology 47:1255-1261.  

2009

Gerlach N, Gibbert K, Alter C, Nair S, Zelinskyy G, James CM, Dittmer U. 2009. Anti-retroviral effects of type I IFN subtypes in vivo. Eur J Immunol 39:136-146.

Zelinskyy G, Dietze KK, Husecken YP, Schimmer S, Nair S, Werner T, Gibbert K, Kershaw O, Gruber AD, Sparwasser T, Dittmer U. 2009. The regulatory T-cell response during acute retroviral infection is locally defined and controls the magnitude and duration of the virus-specific cytotoxic T-cell response. Blood 114:3199-3207.

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