CARD9 Deficiency Increases Hippocampal Injury Following Acute Neurotropic Picornavirus Infection but Does Not Affect Pathogen Elimination
Abstract
:1. Introduction
2. Results
2.1. Loss of CARD9 Promotes Hippocampal Damage Following Virus Infection
2.2. CARD9 Deficiency Transiently Increases the Viral Burden but Does Not Prevent Viral Clearance
2.3. Hippocampal Damage in CARD9−/− Mice Is Associated with an Increased T Cell, B Cell, Regulatory T Cell and M2-Type Myeloid Cell Infiltration
2.4. CARD9−/− Mice Develop Early Pro-Inflammatory Cytokine Responses in the Brain
2.5. CARD9 Deficiency Has a Limited Effect on Initial CD8+ T Cell Responses
2.6. CARD9 Deficiency Does Not Affect Antigen Presenting Cells Ability to Prime CD8+ T Cells Following Theiler’s Murine Encephalomyelitis Virus Infection In Vitro
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Histological and Immunohistochemical Staining
4.3. Real-Time PCR
4.4. Flow Cytometric Immunophenotyping of Murine Splenocytes
4.5. In Vitro T Cell Co-Cultivation
4.6. Statistical Analysis
4.7. Ethic Statement
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Ludlow, M.; Kortekaas, J.; Herden, C.; Hoffmann, B.; Tappe, D.; Trebst, C.; Griffin, D.E.; Brindle, H.E.; Solomon, T.; Brown, A.S.; et al. Neurotropic virus infections as the cause of immediate and delayed neuropathology. Acta Neuropathol. 2016, 131, 159–184. [Google Scholar] [CrossRef] [Green Version]
- Bröer, S.; Hage, E.; Käufer, C.; Gerhauser, I.; Anjum, M.; Li, L.; Baumgärtner, W.; Schulz, T.F.; Löscher, W. Viral mouse models of multiple sclerosis and epilepsy: Marked differences in neuropathogenesis following infection with two naturally occurring variants of Theiler’s virus BeAn strain. Neurobiol. Dis. 2017, 99, 121–132. [Google Scholar] [CrossRef] [PubMed]
- Carson, P.J.; Konewko, P.; Wold, K.S.; Mariani, P.; Goli, S.; Bergloff, P.; Crosby, R.D. Long-term clinical and neuropsychological outcomes of West Nile virus infection. Clin. Infect. Dis. 2006, 43, 723–730. [Google Scholar] [CrossRef]
- Fowler, Å.; Stödberg, T.; Eriksson, M.; Wickström, R. Long-term outcomes of acute encephalitis in childhood. Pediatrics 2010, 126, e828–e835. [Google Scholar] [CrossRef]
- Vezzani, A.; Fujinami, R.S.; White, H.S.; Preux, P.M.; Blumcke, I.; Sander, J.W.; Loscher, W. Infections, inflammation and epilepsy. Acta Neuropathol. 2016, 131, 211–234. [Google Scholar] [CrossRef]
- Betourne, A.; Szelechowski, M.; Thouard, A.; Abrial, E.; Jean, A.; Zaidi, F.; Foret, C.; Bonnaud, E.M.; Charlier, C.M.; Suberbielle, E.; et al. Hippocampal expression of a virus-derived protein impairs memory in mice. Proc. Natl. Acad. Sci. USA 2018, 115, 1611–1616. [Google Scholar] [CrossRef] [Green Version]
- De Chiara, G.; Piacentini, R.; Fabiani, M.; Mastrodonato, A.; Marcocci, M.E.; Limongi, D.; Napoletani, G.; Protto, V.; Coluccio, P.; Celestino, I.; et al. Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice. PLoS Pathog. 2019, 15, e1007617. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cornelius, A.D.A.; Hosseini, S.; Schreier, S.; Fritzsch, D.; Weichert, L.; Michaelsen-Preusse, K.; Fendt, M.; Kroger, A. Langat virus infection affects hippocampal neuron morphology and function in mice without disease signs. J. Neuroinflamm. 2020, 17, 278. [Google Scholar] [CrossRef] [PubMed]
- Theiler, M. Spontaneous encephalomyelitis of mice—A new virus disease. Science 1934, 80, 122. [Google Scholar] [CrossRef] [Green Version]
- Libbey, J.E.; Kirkman, N.J.; Smith, M.C.; Tanaka, T.; Wilcox, K.S.; White, H.S.; Fujinami, R.S. Seizures following picornavirus infection. Epilepsia 2008, 49, 1066–1074. [Google Scholar] [CrossRef] [PubMed]
- Stewart, K.-A.A.; Wilcox, K.S.; Fujinami, R.S.; White, H.S. Development of Post-infection Epilepsy Following Theiler Virus Infection of C57BL/6 Mice. J. Neuropathol. Exp. Neurol. 2010, 69, 1210–1219. [Google Scholar] [CrossRef]
- Buenz, E.J.; Rodriguez, M.; Howe, C.L. Disrupted spatial memory is a consequence of picornavirus infection. Neurobiol. Dis. 2006, 24, 266–273. [Google Scholar] [CrossRef]
- Libbey, J.E.; Fujinami, R.S. Neurotropic viral infections leading to epilepsy: Focus on Theiler’s murine encephalomyelitis virus. Future Virol. 2011, 6, 1339–1350. [Google Scholar] [CrossRef] [Green Version]
- Umpierre, A.D.; Remigio, G.J.; Dahle, E.J.; Bradford, K.; Alex, A.B.; Smith, M.D.; West, P.J.; White, H.S.; Wilcox, K.S. Impaired cognitive ability and anxiety-like behavior following acute seizures in the Theiler’s virus model of temporal lobe epilepsy. Neurobiol. Dis. 2014, 64, 98–106. [Google Scholar] [CrossRef] [Green Version]
- Gerhauser, I.; Hansmann, F.; Ciurkiewicz, M.; Löscher, W.; Beineke, A. Facets of Theiler’s Murine Encephalomyelitis Virus-Induced Diseases: An Update. Int. J. Mol. Sci. 2019, 20, 448. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bowen, J.L.; Olson, J.K. IFNgamma influences type I interferon response and susceptibility to Theiler’s virus-induced demyelinating disease. Viral Immunol. 2013, 26, 223–238. [Google Scholar] [CrossRef] [Green Version]
- Li, L.; Ulrich, R.; Baumgartner, W.; Gerhauser, I. Interferon-stimulated genes-essential antiviral effectors implicated in resistance to Theiler’s virus-induced demyelinating disease. J. Neuroinflamm. 2015, 12, 242. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Drappier, M.; Jha, B.K.; Stone, S.; Elliott, R.; Zhang, R.; Vertommen, D.; Weiss, S.R.; Silverman, R.H.; Michiels, T. A novel mechanism of RNase L inhibition: Theiler’s virus L* protein prevents 2–5A from binding to RNase, L. PLoS Pathog. 2018, 14, e1006989. [Google Scholar] [CrossRef]
- Kirkman, N.J.; Libbey, J.E.; Wilcox, K.S.; White, H.S.; Fujinami, R.S. Innate but not adaptive immune responses contribute to behavioral seizures following viral infection. Epilepsia 2010, 51, 454–464. [Google Scholar] [CrossRef] [Green Version]
- Howe, C.L.; LaFrance-Corey, R.G.; Sundsbak, R.S.; LaFrance, S.J. Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain. J. Neuroinflamm. 2012, 9, 1–13. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Howe, C.L.; Lafrance-Corey, R.G.; Sundsbak, R.S.; Sauer, B.M.; Lafrance, S.J.; Buenz, E.J.; Schmalstieg, W.F. Hippocampal protection in mice with an attenuated inflammatory monocyte response to acute CNS picornavirus infection. Sci. Rep. 2012, 2, 545. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cusick, M.F.; Libbey, J.E.; Patel, D.C.; Doty, D.J.; Fujinami, R.S. Infiltrating macrophages are key to the development of seizures following virus infection. J. Virol. 2013, 87, 1849–1860. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Waltl, I.; Kaufer, C.; Gerhauser, I.; Chhatbar, C.; Ghita, L.; Kalinke, U.; Loscher, W. Microglia have a protective role in viral encephalitis-induced seizure development and hippocampal damage. Brain Behav. Immun. 2018, 74, 186–204. [Google Scholar] [CrossRef] [PubMed]
- Gross, O.; Gewies, A.; Finger, K.; Schäfer, M.; Sparwasser, T.; Peschel, C.; Förster, I.; Ruland, J. Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature 2006, 442, 651–656. [Google Scholar] [CrossRef]
- Robinson, M.J.; Sancho, D.; Slack, E.C.; LeibundGut-Landmann, S.; Reis e Sousa, C. Myeloid C-type lectins in innate immunity. Nat. Immunol. 2006, 7, 1258–1265. [Google Scholar] [CrossRef]
- Mayer, S.; Raulf, M.-K.; Lepenies, B. C-type lectins: Their network and roles in pathogen recognition and immunity. Histochem. Cell Biol. 2017, 147, 223–237. [Google Scholar] [CrossRef]
- Vornholz, L.; Ruland, J. Physiological and Pathological Functions of CARD9 Signaling in the Innate Immune System. Curr. Top. Microbiol. Immunol. 2020, 429, 177–203. [Google Scholar]
- LeibundGut-Landmann, S.; Groß, O.; Robinson, M.J.; Osorio, F.; Slack, E.C.; Tsoni, S.V.; Schweighoffer, E.; Tybulewicz, V.; Brown, G.D.; Ruland, J. Syk-and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat. Immunol. 2007, 8, 630–638. [Google Scholar] [CrossRef]
- Ostrop, J.; Jozefowski, K.; Zimmermann, S.; Hofmann, K.; Strasser, E.; Lepenies, B.; Lang, R. Contribution of MINCLE–SYK signaling to activation of primary human APCs by mycobacterial cord factor and the novel adjuvant TDB. J. Immunol. 2015, 195, 2417–2428. [Google Scholar] [CrossRef] [PubMed]
- Imai, T.; Matsumura, T.; Mayer-Lambertz, S.; Wells, C.A.; Ishikawa, E.; Butcher, S.K.; Barnett, T.C.; Walker, M.J.; Imamura, A.; Ishida, H. Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group A Streptococcus infection. Proc. Natl. Acad. Sci. USA 2018, 115, E10662–E10671. [Google Scholar] [CrossRef] [Green Version]
- Kalantari, P.; Morales, Y.; Miller, E.A.; Jaramillo, L.D.; Ponichtera, H.E.; Wuethrich, M.A.; Cheong, C.; Seminario, M.C.; Russo, J.M.; Bunnell, S.C. CD209a synergizes with Dectin-2 and mincle to drive severe Th17 cell-mediated schistosome egg-induced immunopathology. Cell Rep. 2018, 22, 1288–1300. [Google Scholar] [CrossRef] [Green Version]
- Monteiro, J.T.; Schön, K.; Ebbecke, T.; Goethe, R.; Ruland, J.; Baumgärtner, W.; Becker, S.C.; Lepenies, B. The CARD9-Associated C-Type Lectin, Mincle, Recognizes La Crosse Virus (LACV) but Plays a Limited Role in Early Antiviral Responses against LACV. Viruses 2019, 11, 303. [Google Scholar] [CrossRef] [Green Version]
- Zhao, X.; Chu, H.; Wong, B.H.; Chiu, M.C.; Wang, D.; Li, C.; Liu, X.; Yang, D.; Poon, V.K.; Cai, J.; et al. Activation of C-Type Lectin Receptor and (RIG)-I-Like Receptors Contributes to Proinflammatory Response in Middle East Respiratory Syndrome Coronavirus-Infected Macrophages. J. Infect. Dis. 2020, 221, 647–659. [Google Scholar] [CrossRef]
- Prado Acosta, M.; Goyette-Desjardins, G.; Scheffel, J.; Dudeck, A.; Ruland, J.; Lepenies, B. S-Layer From Lactobacillus brevis Modulates Antigen-Presenting Cell Functions via the Mincle-Syk-Card9 Axis. Front. Immunol. 2021, 12, 511. [Google Scholar] [CrossRef]
- Hsu, Y.-M.S.; Zhang, Y.; You, Y.; Wang, D.; Li, H.; Duramad, O.; Qin, X.-F.; Dong, C.; Lin, X. The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens. Nat. Immunol. 2007, 8, 198–205. [Google Scholar] [CrossRef] [Green Version]
- Poeck, H.; Bscheider, M.; Gross, O.; Finger, K.; Roth, S.; Rebsamen, M.; Hannesschlager, N.; Schlee, M.; Rothenfusser, S.; Barchet, W.; et al. Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production. Nat. Immunol. 2010, 11, 63–69. [Google Scholar] [CrossRef]
- Roth, S.; Rottach, A.; Lotz-Havla, A.S.; Laux, V.; Muschaweckh, A.; Gersting, S.W.; Muntau, A.C.; Hopfner, K.P.; Jin, L.; Vanness, K.; et al. Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1beta production. Nat. Immunol. 2014, 15, 538–545. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Uematsu, T.; Iizasa, E.; Kobayashi, N.; Yoshida, H.; Hara, H. Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity. Sci. Rep. 2015, 5, 17577. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, C.; Zhang, X.; Yu, Y.; Li, Z.; Xie, Y. CARD9 mediates T cell inflammatory response in Coxsackievirus B3-induced acute myocarditis. Cardiovasc. Pathol. 2020, 49, 107261. [Google Scholar] [CrossRef] [PubMed]
- Chang, J.R.; Zaczynska, E.; Katsetos, C.D.; Platsoucas, C.D.; Oleszak, E.L. Differential expression of TGF-beta, IL-2, and other cytokines in the CNS of Theiler’s murine encephalomyelitis virus-infected susceptible and resistant strains of mice. Virology 2000, 278, 346–360. [Google Scholar] [CrossRef] [Green Version]
- Oleszak, E.L.; Chang, J.R.; Friedman, H.; Katsetos, C.D.; Platsoucas, C.D. Theiler’s virus infection: A model for multiple sclerosis. Clin. Microbiol. Rev. 2004, 17, 174–207. [Google Scholar] [CrossRef] [Green Version]
- Monteiro, J.T.; Lepenies, B. Myeloid C-type lectin receptors in viral recognition and antiviral immunity. Viruses 2017, 9, 59. [Google Scholar] [CrossRef]
- Ebbecke, T.; Diersing, C.; Lindenwald, D.L.; Stegmann, F.; Lepenies, B. C-Type Lectins and Their Roles in Disease and Immune Homeostasis. Compr. Glycosci. 2021, 5, 185–214. [Google Scholar]
- Ciurkiewicz, M.; Herder, V.; Khan, M.A.; Uhde, A.K.; Teich, R.; Floess, S.; Baumgärtner, W.; Huehn, J.; Beineke, A. Cytotoxic CD8(+) T cell ablation enhances the capacity of regulatory T cells to delay viral elimination in Theiler’s murine encephalomyelitis. Brain Pathol. 2018, 28, 349–368. [Google Scholar] [CrossRef] [Green Version]
- Getts, M.T.; Kim, B.S.; Miller, S.D. Differential outcome of tolerance induction in naive versus activated Theiler’s virus epitope-specific CD8+ cytotoxic T cells. J. Virol. 2007, 81, 6584–6593. [Google Scholar] [CrossRef] [Green Version]
- Getts, M.T.; Richards, M.H.; Miller, S.D. A critical role for virus-specific CD8(+) CTLs in protection from Theiler’s virus-induced demyelination in disease-susceptible SJL mice. Virology 2010, 402, 102–111. [Google Scholar] [CrossRef] [Green Version]
- Hara, H.; Ishihara, C.; Takeuchi, A.; Imanishi, T.; Xue, L.; Morris, S.W.; Inui, M.; Takai, T.; Shibuya, A.; Saijo, S. The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors. Nat. Immunol. 2007, 8, 619–629. [Google Scholar] [CrossRef] [PubMed]
- Glocker, E.-O.; Hennigs, A.; Nabavi, M.; Schäffer, A.A.; Woellner, C.; Salzer, U.; Pfeifer, D.; Veelken, H.; Warnatz, K.; Tahami, F. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N. Engl. J. Med. 2009, 361, 1727–1735. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gavino, C.; Cotter, A.; Lichtenstein, D.; Lejtenyi, D.; Fortin, C.; Legault, C.; Alirezaie, N.; Majewski, J.; Sheppard, D.C.; Behr, M.A.; et al. CARD9 deficiency and spontaneous central nervous system candidiasis: Complete clinical remission with GM-CSF therapy. Clin. Infect. Dis. 2014, 59, 81–84. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhong, X.; Chen, B.; Yang, L.; Yang, Z. Molecular and physiological roles of the adaptor protein CARD9 in immunity. Cell Death Dis. 2018, 9, 52. [Google Scholar] [CrossRef] [Green Version]
- Drummond, R.A.; Swamydas, M.; Oikonomou, V.; Zhai, B.; Dambuza, I.M.; Schaefer, B.C.; Bohrer, A.C.; Mayer-Barber, K.D.; Lira, S.A.; Iwakura, Y.; et al. CARD9(+) microglia promote antifungal immunity via IL-1beta- and CXCL1-mediated neutrophil recruitment. Nat. Immunol. 2019, 20, 559–570. [Google Scholar] [CrossRef]
- Tsunoda, I.; Kuang, L.-Q.; Libbey, J.E.; Fujinami, R.S. Axonal injury heralds virus-induced demyelination. Am. J. Pathol. 2003, 162, 1259–1269. [Google Scholar] [CrossRef] [Green Version]
- Tsunoda, I. Axonal degeneration as a self-destructive defense mechanism against neurotropic virus infection. Future Med. 2008, 3, 579–593. [Google Scholar] [CrossRef] [Green Version]
- Tsunoda, I.; Tanaka, T.; Terry, E.J.; Fujinami, R.S. Contrasting roles for axonal degeneration in an autoimmune versus viral model of multiple sclerosis: When can axonal injury be beneficial? Am. J. Pathol. 2007, 170, 214–226. [Google Scholar] [CrossRef] [Green Version]
- Jafari, M.; Haist, V.; Baumgartner, W.; Wagner, S.; Stein, V.M.; Tipold, A.; Wendt, H.; Potschka, H. Impact of Theiler’s virus infection on hippocampal neuronal progenitor cells: Differential effects in two mouse strains. Neuropathol. Appl. Neurobiol. 2012, 38, 647–664. [Google Scholar] [CrossRef]
- Bao, Y.; Liu, X.; Han, C.; Xu, S.; Xie, B.; Zhang, Q.; Gu, Y.; Hou, J.; Qian, L.; Qian, C. Identification of IFN-γ-producing innate B cells. Cell Res. 2014, 24, 161–176. [Google Scholar] [CrossRef] [PubMed]
- Dinarello, C.A. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol. Rev. 2018, 281, 8–27. [Google Scholar] [CrossRef] [PubMed]
- Rojas, J.M.; Alejo, A.; Martín, V.; Sevilla, N. Viral pathogen-induced mechanisms to antagonize mammalian interferon (IFN) signaling pathway. Cell. Mol. Life Sci. 2020, 78, 1–22. [Google Scholar] [CrossRef] [PubMed]
- Schmitz, N.; Kurrer, M.; Bachmann, M.F.; Kopf, M. Interleukin-1 is responsible for acute lung immunopathology but increases survival of respiratory influenza virus infection. J. Virol. 2005, 79, 6441–6448. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shrestha, B.; Samuel, M.A.; Diamond, M.S. CD8+ T cells require perforin to clear West Nile virus from infected neurons. J. Virol. 2006, 80, 119–129. [Google Scholar] [CrossRef] [Green Version]
- Pullen, L.C.; Park, S.H.; Miller, S.D.; Dal Canto, M.C.; Kim, B.S. Treatment with bacterial LPS renders genetically resistant C57BL/6 mice susceptible to Theiler’s virus-induced demyelinating disease. J. Immunol. 1995, 155, 4497–4503. [Google Scholar]
- Kim, B.S.; Jin, Y.-H.; Meng, L.; Hou, W.; Kang, H.S.; Park, H.S.; Koh, C.-S. IL-1 signal affects both protection and pathogenesis of virus-induced chronic CNS demyelinating disease. J. Neuroinflamm. 2012, 9, 1–13. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Depino, A.; Ferrari, C.; Pott Godoy, M.C.; Tarelli, R.; Pitossi, F.J. Differential effects of interleukin-1beta on neurotoxicity, cytokine induction and glial reaction in specific brain regions. J. Neuroimmunol. 2005, 168, 96–110. [Google Scholar] [CrossRef] [PubMed]
- Koo, J.W.; Duman, R.S. IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress. Proc. Natl. Acad. Sci. USA 2008, 105, 751–756. [Google Scholar] [CrossRef] [Green Version]
- Pott Godoy, M.C.; Tarelli, R.; Ferrari, C.C.; Sarchi, M.I.; Pitossi, F.J. Central and systemic IL-1 exacerbates neurodegeneration and motor symptoms in a model of Parkinson’s disease. Brain 2008, 131, 1880–1894. [Google Scholar] [CrossRef] [Green Version]
- Prow, N.A.; Irani, D.N. The inflammatory cytokine, interleukin-1 beta, mediates loss of astroglial glutamate transport and drives excitotoxic motor neuron injury in the spinal cord during acute viral encephalomyelitis. J. Neurochem. 2008, 105, 1276–1286. [Google Scholar] [CrossRef]
- Pereira, M.; Tourlomousis, P.; Wright, J.T.P.M.; Bryant, C.E. CARD9 negatively regulates NLRP3-induced IL-1beta production on Salmonella infection of macrophages. Nat. Commun. 2016, 7, 12874. [Google Scholar] [CrossRef] [PubMed]
- Xu, P.; Zhang, X.; Liu, Q.; Xie, Y.; Shi, X.; Chen, J.; Li, Y.; Guo, H.; Sun, R.; Hong, Y. Microglial TREM-1 receptor mediates neuroinflammatory injury via interaction with SYK in experimental ischemic stroke. Cell Death Dis. 2019, 10, 1–17. [Google Scholar] [CrossRef]
- Campuzano, A.; Castro-Lopez, N.; Martinez, A.J.; Olszewski, M.A.; Ganguly, A.; Leopold Wager, C.; Hung, C.Y.; Wormley, F.L., Jr. CARD9 Is Required for Classical Macrophage Activation and the Induction of Protective Immunity against Pulmonary Cryptococcosis. mBio 2020, 11, e03005-19. [Google Scholar] [CrossRef] [Green Version]
- Muraille, E.; Leo, O.; Moser, M. TH1/TH2 paradigm extended: Macrophage polarization as an unappreciated pathogen-driven escape mechanism? Front. Immunol. 2014, 5, 603. [Google Scholar] [CrossRef] [Green Version]
- Richards, M.H.; Getts, M.T.; Podojil, J.R.; Jin, Y.H.; Kim, B.S.; Miller, S.D. Virus expanded regulatory T cells control disease severity in the Theiler’s virus mouse model of MS. J. Autoimmun. 2011, 36, 142–154. [Google Scholar] [CrossRef] [Green Version]
- Martinez, N.E.; Karlsson, F.; Sato, F.; Kawai, E.; Omura, S.; Minagar, A.; Grisham, M.B.; Tsunoda, I. Protective and detrimental roles for regulatory T cells in a viral model for multiple sclerosis. Brain Pathol. 2014, 24, 436–451. [Google Scholar] [CrossRef] [Green Version]
- Daniels, J.B.; Pappenheimer, A.M.; Richardson, S. Observations on encephalomyelitis of mice (DA strain). J. Exp. Med. 1952, 96, 517. [Google Scholar] [CrossRef] [Green Version]
- Falke, D. Über die Züchtung des Theiler-TO-Virus in der Gewebekultur. Zeitschrift für Hygiene und Infektionskrankheiten 1957, 143, 645–655. [Google Scholar] [CrossRef]
- Rabinowitz, S.G.; Lipton, H.L. Cellular immunity in chronic Theiler’s virus central nervous system infection. J. Immunol. 1976, 117, 357–363. [Google Scholar] [PubMed]
- Lipton, H.L. Characterization of the TO strains of Theiler’s mouse encephalomyelitis viruses. Infect. Immun. 1978, 20, 869–872. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kumnok, J.; Ulrich, R.; Wewetzer, K.; Rohn, K.; Hansmann, F.; Baumgärtner, W.; Alldinger, S. Differential transcription of matrix-metalloproteinase genes in primary mouse astrocytes and microglia infected with Theiler’s murine encephalomyelitis virus. J. Neurovirol. 2008, 14, 205–217. [Google Scholar] [CrossRef] [PubMed]
- Käufer, C.; Chhatbar, C.; Bröer, S.; Waltl, I.; Ghita, L.; Gerhauser, I.; Kalinke, U.; Löscher, W. Chemokine receptors CCR2 and CX3CR1 regulate viral encephalitis-induced hippocampal damage but not seizures. Proc. Natl. Acad. Sci. USA 2018, 115, E8929–E8938. [Google Scholar] [CrossRef] [Green Version]
- Waltl, I.; Käufer, C.; Bröer, S.; Chhatbar, C.; Ghita, L.; Gerhauser, I.; Anjum, M.; Kalinke, U.; Löscher, W. Macrophage depletion by liposome-encapsulated clodronate suppresses seizures but not hippocampal damage after acute viral encephalitis. Neurobiol. Dis. 2018, 110, 192–205. [Google Scholar] [CrossRef]
- Paxinos, G.; Franklin, K.B. The Mouse Brain in Stereotaxic Coordinates, 3rd ed.; Paxinos, G., Franklin, K., Eds.; Academic Press: Montreal, QC, Canada, 2007. [Google Scholar]
- Rattka, M.; Brandt, C.; Löscher, W. The intrahippocampal kainate model of temporal lobe epilepsy revisited: Epileptogenesis, behavioral and cognitive alterations, pharmacological response, and hippoccampal damage in epileptic rats. Epilepsy Res. 2013, 103, 135–152. [Google Scholar] [CrossRef]
- Ulrich, R.; Baumgärtner, W.; Gerhauser, I.; Seeliger, F.; Haist, V.; Deschl, U.; Alldinger, S. MMP-12, MMP-3, and TIMP-1 are markedly upregulated in chronic demyelinating theiler murine encephalomyelitis. J. Neuropathol. Exp. Neurol. 2006, 65, 783–793. [Google Scholar] [CrossRef] [Green Version]
- Herder, V.; Hansmann, F.; Stangel, M.; Schaudien, D.; Rohn, K.; Baumgartner, W.; Beineke, A. Cuprizone inhibits demyelinating leukomyelitis by reducing immune responses without virus exacerbation in an infectious model of multiple sclerosis. J. Neuroimmunol. 2012, 244, 84–93. [Google Scholar] [CrossRef]
- Vandesompele, J.; De Preter, K.; Pattyn, F.; Poppe, B.; Van Roy, N.; De Paepe, A.; Speleman, F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002, 3, 1–12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gerhauser, I.; Alldinger, S.; Ulrich, R.; Baumgärtner, W. Spatio-temporal expression of immediate early genes in the central nervous system of SJL/J mice. Int. J. Dev. Neurosci. 2005, 23, 637–649. [Google Scholar] [CrossRef]
- Pavelko, K.D.; Girtman, M.A.; Mitsunaga, Y.; Mendez-Fernandez, Y.V.; Bell, M.P.; Hansen, M.J.; Allen, K.S.; Rodriguez, M.; Pease, L.R. Theiler’s murine encephalomyelitis virus as a vaccine candidate for immunotherapy. PLoS ONE 2011, 6, e20217. [Google Scholar] [CrossRef]
- Pavelko, K.D.; Bell, M.P.; Karyampudi, L.; Hansen, M.J.; Allen, K.S.; Knutson, K.L.; Pease, L.R. The epitope integration site for vaccine antigens determines virus control while maintaining efficacy in an engineered cancer vaccine. Mol. Ther. 2013, 21, 1087–1095. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Prajeeth, C.K.; Beineke, A.; Iskandar, C.D.; Gudi, V.; Herder, V.; Gerhauser, I.; Haist, V.; Teich, R.; Huehn, J.; Baumgärtner, W. Limited role of regulatory T cells during acute Theiler virus-induced encephalitis in resistant C57BL/6 mice. J. Neuroinflamm. 2014, 11, 1–10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
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Pavasutthipaisit, S.; Stoff, M.; Ebbecke, T.; Ciurkiewicz, M.; Mayer-Lambertz, S.; Störk, T.; Pavelko, K.D.; Lepenies, B.; Beineke, A. CARD9 Deficiency Increases Hippocampal Injury Following Acute Neurotropic Picornavirus Infection but Does Not Affect Pathogen Elimination. Int. J. Mol. Sci. 2021, 22, 6982. https://doi.org/10.3390/ijms22136982
Pavasutthipaisit S, Stoff M, Ebbecke T, Ciurkiewicz M, Mayer-Lambertz S, Störk T, Pavelko KD, Lepenies B, Beineke A. CARD9 Deficiency Increases Hippocampal Injury Following Acute Neurotropic Picornavirus Infection but Does Not Affect Pathogen Elimination. International Journal of Molecular Sciences. 2021; 22(13):6982. https://doi.org/10.3390/ijms22136982
Chicago/Turabian StylePavasutthipaisit, Suvarin, Melanie Stoff, Tim Ebbecke, Malgorzata Ciurkiewicz, Sabine Mayer-Lambertz, Theresa Störk, Kevin D. Pavelko, Bernd Lepenies, and Andreas Beineke. 2021. "CARD9 Deficiency Increases Hippocampal Injury Following Acute Neurotropic Picornavirus Infection but Does Not Affect Pathogen Elimination" International Journal of Molecular Sciences 22, no. 13: 6982. https://doi.org/10.3390/ijms22136982