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
  • chronische Virusinfektionen (HIV, HBV)
  • IFN-stimulierte Gene
  • 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 Arbeitsgruppe 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 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

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

 

M.Sc. Rouven-Luca Kaiserling
Rouven-luca.kaiserling@uni-due.de
0201-723-4050

M.Sc. Jonas Schuhenn
Jonas.Schuhenn@uk-essen.de

B. Sc. Mara Schwerdtfeger
0201-723-4050

M. Sc. Zehra Karaköse
0201-723-4050

(MTA)

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

Ausgewählte Publikationen

2020

Ickler, J., Francois, S., Widera, M., Santiago, M.L., Dittmer, U., Sutter, K., 2020. HIV infection does not alter interferon alpha/beta receptor 2 expression on mucosal immune cells. PLoS One 15, e0218905.

Zutz, A., Scholz, C., Schneider, S., Pierini, V., Munchhoff, M., Sutter, K., Wittmann, G., Dittmer, U., Draenert, R., Bogner, J.R., Fackler, O.T., Keppler, O.T., 2020. SERINC5 Is an Unconventional HIV Restriction Factor That Is Upregulated during Myeloid Cell Differentiation. J Innate Immun, 1-11.

 

2019

Sutter, K., Lavender, K.J., Messer, R.J., Widera, M., Williams, K., Race, B., Hasenkrug, K.J., Dittmer, U., 2019. Concurrent administration of IFNalpha14 and cART in TKO-BLT mice enhances suppression of HIV-1 viremia but does not eliminate the latent reservoir. Sci Rep 9, 18089.

Dickow, J., Francois, S., Kaiserling, R.L., Malyshkina, A., Drexler, I., Westendorf, A.M., Lang, K.S., Santiago, M.L., Dittmer, U., Sutter, K., 2019. Diverse Immunomodulatory Effects of Individual IFNalpha Subtypes on Virus-Specific CD8(+) T Cell Responses. Front Immunol 10, 2255.

Braun, E., Hotter, D., Koepke, L., Zech, F., Gross, R., Sparrer, K.M.J., Muller, J.A., Pfaller, C.K., Heusinger, E., Wombacher, R., Sutter, K., Dittmer, U., Winkler, M., Simmons, G., Jakobsen, M.R., Conzelmann, K.K., Pohlmann, S., Munch, J., Fackler, O.T., Kirchhoff, F., Sauter, D., 2019. Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins. Cell Rep 27, 2092-2104 e2010.

Dittmer, U., Sutter, K., Kassiotis, G., Zelinskyy, G., Banki, Z., Stoiber, H., Santiago, M.L., Hasenkrug, K.J., 2019. Friend retrovirus studies reveal complex interactions between intrinsic, innate and adaptive immunity. FEMS Microbiol Review 43, 435-456.

Gujer, C., Murer, A., Muller, A., Vanoaica, D., Sutter, K., Jacque, E., Fournier, N., Kalchschmidt, J., Zbinden, A., Capaul, R., Dzionek, A., Mondon, P., Dittmer, U., Munz, C., 2019. Plasmacytoid dendritic cells respond to Epstein-Barr virus infection with a distinct type I interferon subtype profile. Blood Adv 3, 1129-1144.

Hasenkrug, K.J., Lavender, K.J., Santiago, M.L., Sutter, K., Dittmer, U., 2019. Different Biological Activities of Specific Interferon Alpha Subtypes. mSphere 4.

Malyshkina, A., Littwitz-Salomon, E., Sutter, K., Ross, J.A., Paschen, A., Windmann, S., Schimmer, S., Dittmer, U., 2019. Chronic retroviral infection of mice promotes tumor development, but CD137 agonist therapy restores effective tumor immune surveillance. Cancer Immunol Immunother 68, 479-488.

Matos, A.D.R., Wunderlich, K., Schloer, S., Schughart, K., Geffers, R., Seders, M., Witt, M., Christersson, A., Wiewrodt, R., Wiebe, K., Barth, P., Hocke, A., Hippenstiel, S., Honzke, K., Dittmer, U., Sutter, K., Rescher, U., Rodionycheva, S., Matera, N., Ludwig, S., Brunotte, L., 2019. Antiviral potential of human IFN-alpha subtypes against influenza A H3N2 infection in human lung explants reveals subtype-specific activities. Emerg Microbes Infect 8, 1763-1776.

Passos, V., Zillinger, T., Casartelli, N., Wachs, A.S., Xu, S., Malassa, A., Steppich, K., Schilling, H., Franz, S., Todt, D., Steinmann, E., Sutter, K., Dittmer, U., Bohne, J., Schwartz, O., Barchet, W., Goffinet, C., 2019. Characterization of Endogenous SERINC5 Protein as Anti-HIV-1 Factor. J Virol 93.

Xia, Y., Schlapschy, M., Morath, V., Roeder, N., Vogt, E.I., Stadler, D., Cheng, X., Dittmer, U., Sutter, K., Heikenwalder, M., Skerra, A., Protzer, U., 2019. PASylated interferon alpha efficiently suppresses hepatitis B virus and induces anti-HBs seroconversion in HBV-transgenic mice. Antiviral Res 161, 134-143.

 

2018

Lavender, K.J., Pace, C., Sutter, K., Messer, R.J., Pouncey, D.L., Cummins, N.W., Natesampillai, S., Zheng, J., Goldsmith, J., Widera, M., Van Dis, E.S., Phillips, K., Race, B., Dittmer, U., Kukolj, G., Hasenkrug, K.J., 2018. An advanced BLT-humanized mouse model for extended HIV-1 cure studies. AIDS 32, 1-10.

Knuschke, T., Rotan, O., Bayer, W., Kollenda, S., Dickow, J., Sutter, K., Hansen, W., Dittmer, U., Lang, K.S., Epple, M., Buer, J., Westendorf, A.M., 2018. Induction of Type I Interferons by Therapeutic Nanoparticle-Based Vaccination Is Indispensable to Reinforce Cytotoxic CD8(+) T Cell Responses During Chronic Retroviral Infection. Front Immunol 9, 614.

Korth, J., Anastasiou, O.E., Verheyen, J., Dickow, J., Sertznig, H., Frericks, N., Bleekmann, B., Kribben, A., Brinkhoff, A., Wilde, B., Sutter, K., Dittmer, U., Ciesek, S., Witzke, O., Widera, M., 2018. Impact of immune suppressive agents on the BK-Polyomavirus non coding control region. Antiviral Res 159, 68-76.

Shen, F., Li, Y., Wang, Y., Sozzi, V., Revill, P.A., Liu, J., Gao, L., Yang, G., Lu, M., Sutter, K., Dittmer, U., Chen, J., Yuan, Z., 2018. Hepatitis B virus sensitivity to interferon-alpha in hepatocytes is more associated with cellular interferon response than with viral genotype. Hepatology 67, 1237-1252.

Sutter, K., Dickow, J., Dittmer, U., 2018. Interferon alpha subtypes in HIV infection. Cytokine Growth Factor Review 40, 13-18.

 

2017

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.

Ziegler, S.M., Beisel, C., Sutter, K., Griesbeck, M., Hildebrandt, H., Hagen, S.H., Dittmer, U., Altfeld, M., 2017. Human pDCs display sex-specific differences in type I interferon subtypes and interferon alpha/beta receptor expression. Eur J Immunol 47, 251-256.

Li, Y., Sun, B., Esser, S., Jessen, H., Streeck, H., Widera, M., Yang, R., Dittmer, U., Sutter, K., 2017. Expression Pattern of Individual IFNA Subtypes in Chronic HIV Infection. J Interferon Cytokine Res 37, 541-549.

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

Schreiber, T., Quinting, T., Dittmer, U., Fandrey, J., Sutter, K., 2017. Hypoxia-inducible factor 1alpha is Essential for Macrophage-mediated Erythroblast Proliferation in Acute Friend Retrovirus Infection. Sci Rep 7, 17236.

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.

 

2016

Lavender, K.J., Gibbert, K., Peterson, K.E., Van Dis, E., Francois, S., Woods, T., Messer, R.J., Gawanbacht, A., Muller, J.A., Munch, J., Phillips, K., Race, B., Harper, M.S., Guo, K., Lee, E.J., Trilling, M., Hengel, H., Piehler, J., Verheyen, J., Wilson, C.C., Santiago, M.L., Hasenkrug, K.J., Dittmer, U., 2016. Interferon Alpha Subtype-Specific Suppression of HIV-1 Infection In Vivo. J Virol 90, 6001-6013.

Li, S.X., Barrett, B.S., Guo, K., Kassiotis, G., Hasenkrug, K.J., Dittmer, U., Gibbert, K., Santiago, M.L., 2016. Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection. Scientific reports 6, 20425.

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.

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. Review.

Real, C.I., Lu, M., Liu, J., Huang, X., Trippler, M., Hossbach, M., Deckert, J., Jahn-Hofmann, K., Ickenstein, L.M., John, M.J., Gibbert, K., Dittmer, U., Vornlocher, H.P., Schirmbeck, R., Gerken, G., Schlaak, J.F., 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, C.P., Gibbert, K., Dietze, K.K., Werner, T., Liu, J., Chen, L., Lang, K.S., Palmer, B.E., Dittmer, U., Zelinskyy, G., 2015a. Correction: PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing. PLoS pathogens 11, e1005364.

Harper, M.S., Guo, K., Gibbert, K., Lee, E.J., Dillon, S.M., Barrett, B.S., McCarter, M.D., Hasenkrug, K.J., Dittmer, U., Wilson, C.C., Santiago, M.L., 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, K.K., Gibbert, K., Lang, K.S., 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. Sci Rep 5, 10501.

 

2014

Xu, H.C., Grusdat, M., Pandyra, A.A., 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, T.W., Ohashi, P.S., Lang, K.S., Lang, P.A., 2014. Type I interferon protects antiviral CD8+ T cells from NK cell cytotoxicity. Immunity 40, 949-960.

Broering, R., Real, C.I., John, M.J., Jahn-Hofmann, K., Ickenstein, L.M., Kleinehr, K., Paul, A., Gibbert, K., Dittmer, U., Gerken, G., Schlaak, J.F., 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.

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.

 

2013

Behrendt, R., Schumann, T., Gerbaulet, A., Nguyen, L.A., 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 Rep.

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

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. Review.

Harper, M.S., Barrett, B.S., Smith, D.S., Li, S.X., Gibbert, K., Dittmer, U., Hasenkrug, K.J., Santiago, M.L., 2013. IFN-alpha treatment inhibits acute Friend retrovirus replication primarily through the antiviral effector molecule Apobec3. Journal of immunology 190, 1583-1590.

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.

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. Biol Chem 394, 495-505.

 

2012

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

 

2011

Dietze, K.K., Zelinskyy, G., Gibbert, K., Schimmer, S., Francois, S., Myers, L., Sparwasser, T., Hasenkrug, K.J., 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.

Gibbert, K., Francois, S., Sigmund, A.M., Harper, M.S., Barrett, B.S., Kirchning, C.J., Lu, M., Santiago, M.L., Dittmer, U., 2014. Friend retrovirus drives cytotoxic effectors through Toll-like receptor 3. Retrovirology 11, 1.

Zelinskyy, G., Myers, L., Dietze, K.K., Gibbert, K., Roggendorf, M., Liu, J., Lu, M., Kraft, A.R., Teichgraber, V., Hasenkrug, K.J., 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.

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

 

2010

Gibbert, K., Dietze, K.K., Zelinskyy, G., Lang, K.S., Barchet, W., Kirschning, C.J., 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, L.Y., Gibbert, K., Suezer, Y., Radeke, H.H., 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, C.M., Dittmer, U., 2009. Anti-retroviral effects of type I IFN subtypes in vivo. Eur J Immunol 39, 136-146.

Zelinskyy, G., Dietze, K.K., Husecken, Y.P., Schimmer, S., Nair, S., Werner, T., Gibbert, K., Kershaw, O., Gruber, A.D., 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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