Innate Immunity and Infection

The moment a pathogen, which has successfully entered the body, is recognized, the body quickly mobilizes its defenses. Interferons are molecules that are counted among the body’s first line of defense. They prevent proliferation and the spread of viruses in the body and serve to alert the immune system. Read here about the different ways we use to try and decode this system, all in an effort to find new approaches to infectious disease prevention and therapy.

Leader

Selected Publications

Kurhade C, Schreier S, Lee YP, Zegenhagen L, Hjertqvist M, Dobler G, Kröger A, Överby AK. Correlation of Severity of Human Tick-Borne Encephalitis Virus Disease and Pathogenicity in Mice.
Emerg Infect Dis. 2018 Sep;24(9):1709-1712. doi: 10.3201/eid2409.171825.

Kurhade C, Zegenhagen L, Weber E, Nair S, Michaelsen-Preusse K, Spanier J, Gekara NO, Kröger A*, Overby AK*. 2016. Type I Interferon response in olfactory bulb, the site of tick-borne flavivirus accumulation, is primarily regulated by IPS-1. J Neuroinflammation 13:22.

Nair S, Michaelsen-Preusse K, Finsterbusch K, Stegemann-Koniszewski S, Bruder D, Grashoff M, Korte M, Koster M, Kalinke U, Hauser H, Kröger A. 2014. Interferon regulatory factor-1 protects from fatal neurotropic infection with vesicular stomatitis virus by specific inhibition of viral replication in neurons. PLoS Pathog 10:e1003999.

Weber E, Finsterbusch K, Lindquist R, Nair S, Lienenklaus S, Gekara NO, Janik D, Weiss S, Kalinke U, Overby AK, Kröger A. 2014. Type I interferon protects mice from fatal neurotropic infection with Langat virus by systemic and local antiviral responses. J Virol 88:12202-12212.

Nandakumar R, Finsterbusch K, Lipps C, Neumann B, Grashoff M, Nair S, Hochnadel I, Lienenklaus S, Wappler I, Steinmann E, Hauser H, Pietschmann T, Kröger A. 2013. Hepatitis C virus replication in mouse cells is restricted by IFN-dependent and -independent mechanisms. Gastroenterology 145:1414-1423.e1411.

Publications

2019

Ring S, Eggers L, Behrends J, Wutkowski A, Schwudke D, Kröger A, Hierweger AM, Hölscher C, Gabriel G, Schneider BE. Blocking IL-10 receptor signaling ameliorates Mycobacterium tuberculosis infection during influenza-induced exacerbation. JCI Insight. 2019 Apr 18;5. pii: 126533. doi: 10.1172/jci.insight.126533.

Büssow K, Themann P, Luu S, Pentrowski P, Harting C, Majewski M, Vollmer V, Köster M, Grashoff M, Zawatzky R, Van den Heuvel J, Kröger A, Böldicke T. ER intrabody-mediated inhibition of interferon α secretion by mouse macrophages and dendritic cells. PLoS One. 2019 Apr 16;14(4):e0215062. doi: 10.1371/journal.pone.0215062. eCollection 2019.

2018

Kurhade C, Schreier S, Lee YP, Zegenhagen L, Hjertqvist M, Dobler G, Kröger A, Överby AK. Correlation of Severity of Human Tick-Borne Encephalitis Virus Disease and Pathogenicity in Mice.
Emerg Infect Dis. 2018 Sep;24(9):1709-1712. doi: 10.3201/eid2409.171825.

Eyer L, Kondo H, Zouharova D, Hirano M, Valdés JJ, Muto M, Kastl T, Kobayashi S, Haviernik J, Igarashi M, Kariwa H, Vaculovicova M, Cerny J, Kizek R, Kröger A, Lienenklaus S, Dejmek M, Nencka R, Palus M, Salat J, De Clercq E, Yoshii K, Ruzek D. Escape of tick-borne flavivirus from 2' -C-methylated nucleoside antivirals is mediated by a single conservative mutation in NS5 that has a dramatic effect on viral fitness. J Virol. 2017 Aug 16. pii: JVI.01028-17. doi: 10.1128/JVI.01028-17. [Epub ahead of print]

Kröger A. IRFs as competing pioneers in T-cell differentiation. Cell Mol Immunol. 2017 Aug;14(8):649-651. doi: 10.1038/cmi.2017.37. Epub  2017 Jun 19.

Somplatzki S, Mühlenhoff M, Kröger A, Gerardy-Schahn R, Böldicke T. Intrabodies against the Polysialyltransferases ST8SiaII and ST8SiaIV inhibit Polysialylation of NCAM in rhabdomyosarcoma tumor cells. BMC Biotechnol. 2017 May 12;17(1):42. doi: 10.1186/s12896-017-0360-7.

2017

Eyer L, Kondo H, Zouharova D, Hirano M, Valdes JJ, Muto M, Kastl T, Kobayashi S, Haviernik J, Igarashi M, Kariwa H, Vaculovicova M, Cerny J, Kizek R, Kröger A, Lienenklaus S, Dejmek M, Nencka R, Palus M, Salat J, De Clercq E, Yoshii K, Ruzek D. 2017. Escape of tick-borne flavivirus from 2' -C-methylated nucleoside antivirals is mediated by a single conservative mutation in NS5 that has a dramatic effect on viral fitness. J Virol doi:10.1128/jvi.01028-17.

Kröger A. 2017. IRFs as competing pioneers in T-cell differentiation. Cell Mol Immunol 14:649-651.

Somplatzki S, Muhlenhoff M, Kröger A, Gerardy-Schahn R, Boldicke T. 2017. Intrabodies against the Polysialyltransferases ST8SiaII and ST8SiaIV inhibit Polysialylation of NCAM in rhabdomyosarcoma tumor cells. BMC Biotechnol 17:42.

2016

Kurhade C, Zegenhagen L, Weber E, Nair S, Michaelsen-Preusse K, Spanier J, Gekara NO, Kröger A, Overby AK. 2016. Type I Interferon response in olfactory bulb, the site of tick-borne flavivirus accumulation, is primarily regulated by IPS-1. J Neuroinflammation 13:22.

Asghar N, Lee YP, Nilsson E, Lindqvist R, Melik W, Kröger A, Overby AK, Johansson M. 2016. The role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus. Sci Rep 6:39265.

Lindqvist R, Mundt F, Gilthorpe JD, Wolfel S, Gekara NO, Kröger A, Overby AK. 2016. Fast type I interferon response protects astrocytes from flavivirus infection and virus-induced cytopathic effects. J Neuroinflammation 13:277.

Stegemann-Koniszewski S, Jeron A, Gereke M, Geffers R, Kröger A, Gunzer M, Bruder D. 2016. Alveolar Type II Epithelial Cells Contribute to the Anti-Influenza A Virus Response in the Lung by Integrating Pathogen- and Microenvironment-Derived Signals. MBio 7.

Castiglia V, Piersigilli A, Ebner F, Janos M, Goldmann O, Dambock U, Kröger A, Weiss S, Knapp S, Jamieson AM, Kirschning C, Kalinke U, Strobl B, Muller M, Stoiber D, Lienenklaus S, Kovarik P. 2016. Type I Interferon Signaling Prevents IL-1beta-Driven Lethal Systemic Hyperinflammation during Invasive Bacterial Infection of Soft Tissue. Cell Host Microbe 19:375-387.

Andzinski L, Spanier J, Kasnitz N, Kröger A, Jin L, Brinkmann MM, Kalinke U, Weiss S, Jablonska J, Lienenklaus S. 2016. Growing tumors induce a local STING dependent Type I IFN response in dendritic cells. Int J Cancer 139:1350-1357.

Zegenhagen L, Kurhade C, Koniszewski N, Overby AK, Kröger A. 2016. Brain heterogeneity leads to differential innate immune responses and modulates pathogenesis of viral infections. Cytokine Growth Factor Rev 30:95-101.

Nocera DA, Roselli E, Araya P, Nunez NG, Lienenklaus S, Jablonska J, Weiss S, Gatti G, Brinkmann MM, Kröger A, Moron G, Maccioni M. 2016. In Vivo Visualizing the IFN-beta Response Required for Tumor Growth Control in a Therapeutic Model of Polyadenylic-Polyuridylic Acid Administration. J Immunol 196:2860-2869.

2015

Hartlova A, Erttmann SF, Raffi FA, Schmalz AM, Resch U, Anugula S, Lienenklaus S, Nilsson LM, Kröger A, Nilsson JA, Ek T, Weiss S, Gekara NO. 2015. DNA damage primes the type I interferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity. Immunity 42:332-343.

Marandu TF, Oduro JD, Borkner L, Dekhtiarenko I, Uhrlaub JL, Drabig A, Kröger A, Nikolich-Zugich J, Cicin-Sain L. 2015. Immune Protection against Virus Challenge in Aging Mice Is Not Affected by Latent Herpesviral Infections. J Virol 89:11715-11717.

Wu CF, Andzinski L, Kasnitz N, Kröger A, Klawonn F, Lienenklaus S, Weiss S, Jablonska J. 2015. The lack of type I interferon induces neutrophil-mediated pre-metastatic niche formation in the mouse lung. Int J Cancer 137:837-847.

Andzinski L, Wu CF, Lienenklaus S, Kröger A, Weiss S, Jablonska J. 2015. Delayed apoptosis of tumor associated neutrophils in the absence of endogenous IFN-beta. Int J Cancer 136:572-583.

2014

Nair S, Michaelsen-Preusse K, Finsterbusch K, Stegemann-Koniszewski S, Bruder D, Grashoff M, Korte M, Koster M, Kalinke U, Hauser H, Kröger A. 2014. Interferon regulatory factor-1 protects from fatal neurotropic infection with vesicular stomatitis virus by specific inhibition of viral replication in neurons. PLoS Pathog 10:e1003999.

Weber E, Finsterbusch K, Lindquist R, Nair S, Lienenklaus S, Gekara NO, Janik D, Weiss S, Kalinke U, Overby AK, Kröger A. 2014. Type I interferon protects mice from fatal neurotropic infection with Langat virus by systemic and local antiviral responses. J Virol 88:12202-12212.

Spanier J, Lienenklaus S, Paijo J, Kessler A, Borst K, Heindorf S, Baker DP, Kröger A, Weiss S, Detje CN, Staeheli P, Kalinke U. 2014. Concomitant TLR/RLH signaling of radioresistant and radiosensitive cells is essential for protection against vesicular stomatitis virus infection. J Immunol 193:3045-3054.

Marandu TF, Finsterbusch K, Kröger A, Cicin-Sain L. 2014. Mouse CMV infection delays antibody class switch upon an unrelated virus challenge. Exp Gerontol 54:101-108.

Frentzen A, Anggakusuma, Gurlevik E, Hueging K, Knocke S, Ginkel C, Brown RJ, Heim M, Dill MT, Kröger A, Kalinke U, Kaderali L, Kuehnel F, Pietschmann T. 2014. Cell entry, efficient RNA replication, and production of infectious hepatitis C virus progeny in mouse liver-derived cells. Hepatology 59:78-88.

2013

Nandakumar R, Finsterbusch K, Lipps C, Neumann B, Grashoff M, Nair S, Hochnadel I, Lienenklaus S, Wappler I, Steinmann E, Hauser H, Pietschmann T, Kröger A. 2013. Hepatitis C virus replication in mouse cells is restricted by IFN-dependent and -independent mechanisms. Gastroenterology 145:1414-1423.e1411.

2012

Ksienzyk A, Neumann B, Kröger A. 2012. IRF-1 is critical for IFNgamma mediated immune surveillance. Oncoimmunology 1:533-534.

Rand U, Rinas M, Schwerk J, Nohren G, Linnes M, Kröger A, Flossdorf M, Kaly-Kullai K, Hauser H, Hofer T, Koster M. 2012. Multi-layered stochasticity and paracrine signal propagation shape the type-I interferon response. Mol Syst Biol 8:584.

2011

Ksienzyk A, Neumann B, Nandakumar R, Finsterbusch K, Grashoff M, Zawatzky R, Bernhardt G, Hauser H, Kröger A. 2011. IRF-1 expression is essential for natural killer cells to suppress metastasis. Cancer Res 71:6410-6418.

2010

Stirnweiss A, Ksienzyk A, Klages K, Rand U, Grashoff M, Hauser H, Kröger A. 2010. IFN regulatory factor-1 bypasses IFN-mediated antiviral effects through viperin gene induction. J Immunol 184:5179-5185.

Dietrich N, Rohde M, Geffers R, Kröger A, Hauser H, Weiss S, Gekara NO. 2010. Mast cells elicit proinflammatory but not type I interferon responses upon activation of TLRs by bacteria. Proc Natl Acad Sci U S A 107:8748-8753.

2009

Probst-Kepper M, Geffers R, Kröger A, Viegas N, Erck C, Hecht HJ, Lunsdorf H, Roubin R, Moharregh-Khiabani D, Wagner K, Ocklenburg F, Jeron A, Garritsen H, Arstila TP, Kekalainen E, Balling R, Hauser H, Buer J, Weiss S. 2009. GARP: a key receptor controlling FOXP3 in human regulatory T cells. J Cell Mol Med 13:3343-3357.

Stegemann S, Dahlberg S, Kröger A, Gereke M, Bruder D, Henriques-Normark B, Gunzer M. 2009. Increased susceptibility for superinfection with Streptococcus pneumoniae during influenza virus infection is not caused by TLR7-mediated lymphopenia. PLoS One 4:e4840.

Probst-Kepper M, Kröger A, Garritsen HS, Buer J. 2009. Perspectives on Regulatory T Cell Therapies. Transfus Med Hemother 36:302-308.

2008

Bochtler P, Kröger A, Schirmbeck R, Reimann J. 2008. Type I IFN-induced, NKT cell-mediated negative control of CD8 T cell priming by dendritic cells. J Immunol 181:1633-1643.

2007

Kröger A, Stirnweiss A, Pulverer JE, Klages K, Grashoff M, Reimann J, Hauser H. 2007. Tumor suppression by IFN regulatory factor-1 is mediated by transcriptional down-regulation of cyclin D1. Cancer Res 67:2972-2981.

Ramsauer K, Farlik M, Zupkovitz G, Seiser C, Kröger A, Hauser H, Decker T. 2007. Distinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-gamma-inducible gbp2 gene. Proc Natl Acad Sci U S A 104:2849-2854.

2006

Schirmbeck R, Riedl P, Kupferschmitt M, Wegenka U, Hauser H, Rice J, Kröger A, Reimann J. 2006. Priming protective CD8 T cell immunity by DNA vaccines encoding chimeric, stress protein-capturing tumor-associated antigen. J Immunol 177:1534-1542.

Froese N, Schwarzer M, Niedick I, Frischmann U, Koster M, Kröger A, Mueller PP, Nourbakhsh M, Pasche B, Reimann J, Staeheli P, Hauser H. 2006. Innate immune responses in NF-kappaB-repressing factor-deficient mice. Mol Cell Biol 26:293-302.

2005

May T, Mueller PP, Weich H, Froese N, Deutsch U, Wirth D, Kröger A, Hauser H. 2005. Establishment of murine cell lines by constitutive and conditional immortalization. J Biotechnol 120:99-110.

Dikopoulos N, Bertoletti A, Kröger A, Hauser H, Schirmbeck R, Reimann J. 2005. Type I IFN negatively regulates CD8+ T cell responses through IL-10-producing CD4+ T regulatory 1 cells. J Immunol 174:99-109.

2004

Dikopoulos N, Wegenka U, Kröger A, Hauser H, Schirmbeck R, Reimann J. 2004. Recently primed CD8+ T cells entering the liver induce hepatocytes to interact with naive CD8+ T cells in the mouse. Hepatology 39:1256-1266.

Jomantaite I, Dikopoulos N, Kröger A, Leithauser F, Hauser H, Schirmbeck R, Reimann J. 2004. Hepatic dendritic cell subsets in the mouse. Eur J Immunol 34:355-365.

2003

Kwissa M, Kröger A, Hauser H, Reimann J, Schirmbeck R. 2003. Cytokine-facilitated priming of CD8+ T cell responses by DNA vaccination. J Mol Med (Berl) 81:91-101.

2002

Trobonjaca Z, Kröger A, Stober D, Leithauser F, Moller P, Hauser H, Schirmbeck R, Reimann J. 2002. Activating immunity in the liver. II. IFN-beta attenuates NK cell-dependent liver injury triggered by liver NKT cell activation. J Immunol 168:3763-3770.

Kröger A, Koster M, Schroeder K, Hauser H, Mueller PP. 2002. Activities of IRF-1. J Interferon Cytokine Res 22:5-14.

2001

Unsinger J, Kröger A, Hauser H, Wirth D. 2001. Retroviral vectors for the transduction of autoregulated, bidirectional expression cassettes. Mol Ther 4:484-489.

Hennecke M, Kwissa M, Metzger K, Oumard A, Kröger A, Schirmbeck R, Reimann J, Hauser H. 2001. Composition and arrangement of genes define the strength of IRES-driven translation in bicistronic mRNAs. Nucleic Acids Res 29:3327-3334.

Kröger A, Ortmann D, Krohne TU, Mohr L, Blum HE, Hauser H, Geissler M. 2001. Growth suppression of the hepatocellular carcinoma cell line Hepa1-6 by an activatable interferon regulatory factor-1 in mice. Cancer Res 61:2609-2617.

2000

Schirmbeck R, von Kampen J, Metzger K, Wild J, Gruner B, Schleef M, Kröger A, Hauser H, Reimann J. 2000. DNA-Based Vaccination with Polycistronic Expression Plasmids. Methods Mol Med 29:313-322.

1998

Yakimov MM, Kröger A, Slepak TN, Giuliano L, Timmis KN, Golyshin PN. 1998. A putative lichenysin A synthetase operon in Bacillus licheniformis: initial characterization. Biochim Biophys Acta 1399:141-153.

1996

Kirchhoff S, Kröger A, Cruz H, Tummler M, Schaper F, Koster M, Hauser H. 1996. Regulation of cell growth by IRF-1 in BHK-21 cells. Cytotechnology 22:147-156.

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