European Journal of Microbiology and Immunology
Volume/Issue:
Volume 4: Issue 1
Spinal cord pathology in chronic experimental Toxoplasma gondii infection
Authors:
L. Möhle Institute of Medical Microbiology, Otto-von-Guericke University Magdeburg, Magdeburg, Leipziger Straße 44, Building 44, 39120, Germany

Search for other papers by L. Möhle in
Current site
Google Scholar
PubMed Close
,
A. Parlog Institute of Medical Microbiology, Otto-von-Guericke University Magdeburg, Magdeburg, Leipziger Straße 44, Building 44, 39120, Germany

Search for other papers by A. Parlog in
Current site
Google Scholar
PubMed Close
,
J. Pahnke Neurodegeneration Research Lab (NRL), Department of Neurology, University of Magdeburg, Magdeburg, Germany
German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Leipziger Str. 44, Building 64, 39120, Germany

Search for other papers by J. Pahnke in
Current site
Google Scholar
PubMed Close
, and
Ildiko Rita Dunay Institute of Medical Microbiology, Otto-von-Guericke University Magdeburg, Magdeburg, Leipziger Straße 44, Building 44, 39120, Germany

Search for other papers by Ildiko Rita Dunay in
Current site
Google Scholar
PubMed Close
Pages:
65–75
Online Publication Date:
01 Mar 2014
Publication Date:
01 Mar 2014
Article Category:
Research Article
DOI:
https://doi.org/10.1556/eujmi.4.2014.1.6
Keywords:
Toxoplasma gondii ; spinal cord; inflammation; infection; myelitis
Restricted access

Abstract

Infection with the protozoan Toxoplasma (T.) gondii causes chronic infection of the central nervous system and can lead to lifethreatening encephalomyelitis in immunocompromised patients. While infection with T. gondii has long time been considered asymptomatic in immunocompetent hosts, this view is challenged by recent reports describing links between seropositivity and behavioral alterations.

However, past and current researches are mainly focused on the brain during Toxoplasma encephalitis, neglecting the spinal cord as a key structure conveying brain signals into motion. Therefore, our study aimed to fill the gap and describes the spinal cord pathology in an experimental murine model of toxoplasmosis.

In the spinal cord, we found distinct histopathological changes, inflammatory foci and T. gondii cysts similar to the brain. Furthermore, the recruitment of immune cells from the periphery was detected. Moreover, resident microglia as well as recruited monocytes displayed an increased MHC classes I and II expression. Additionally, the expression of pro- and anti-inflammatory cytokines was enhanced in the brain as well as in the spinal cord. In summary, the pathology observed in the spinal cord was similar to the previously described changes in the brain during the infection.

This study provides the first detailed description of histopathological and immunological alterations due to experimental T. gondii induced myelitis in mice. Thus, our comparison raises awareness of the importance of the spinal cord in chronic T. gondii infection.

  • 1. A.M. Tenter A.R. Heckeroth L.M. Weiss 2000 Toxoplasma gondii: from animals to humans Int J Parasitol 30 1217 1258.

  • 2. J.G. Montoya O. Liesenfeld 2004 Toxoplasmosis Lancet 363 1965 1976.

  • 3. D.J. Ferguson D.I. Graham W.M. Hutchison 1991 Pathological changes in the brains of mice infected with Toxoplasma gondii: a histological, immunocytochemical and ultrastructural study Int J Exp Pathol 72 463 474.

    • Search Google Scholar
    • Export Citation

  • 4. J.P. Dubey 2009 History of the discovery of the life cycle of Toxoplasma gondii Int J Parasitol 39 877 882.

  • 5. L.M. Randall C.A. Hunter 2011 Parasite dissemination and the pathogenesis of toxoplasmosis Eur J Microbiol Immunol 1 3 9.

  • 6. R.M. Quencer M.J. Post 1997 Spinal cord lesions in patients with AIDS Neuroimaging Clin N Am 7 359 373.

  • 7. E. Maciel I. Siqueira A.C. Queiroz A. Melo 2000 Toxoplasma gondii myelitis in a patient with adult T-cell leukemia-lymphoma Arq Neuropsiquiatr 58 1107 1109.

    • Search Google Scholar
    • Export Citation

  • 8. C.S. Straathof L.M. Kortbeek H. Roerdink P.A. Sillevis Smitt M.J. van den Bent 2001 A solitary spinal cord toxoplasma lesion after peripheral stem-cell transplantation J Neurol 248 814 815.

    • Search Google Scholar
    • Export Citation

  • 9. C.K. Fairley J. Wodak E. Benson 1992 Spinal cord toxoplasmosis in a patient with human immunodeficiency virus infection Int J STD AIDS 3 366 368.

    • Search Google Scholar
    • Export Citation

  • 10. D.K. Resnick 1995 Isolated toxoplasmosis of the thoracic spinal cord in a patient with acquired immunodeficiency syndrome Case report. J Neurosurg 82 493 496.

    • Search Google Scholar
    • Export Citation

  • 11. R. Vyas J.R. Ebright 1996 Toxoplasmosis of the spinal cord in a patient with AIDS: case report and review Clin Infect Dis 23 1061 1065.

    • Search Google Scholar
    • Export Citation

  • 12. D.H. Kung 2011 Toxoplasmosis myelopathy and myopathy in an AIDS patient: a case of immune reconstitution inflammatory syndrome Neurologist 17 49 51.

    • Search Google Scholar
    • Export Citation

  • 13. J.R. Heidel 1990 Myelitis in a cat infected with Toxoplasma gondii and feline immunodeficiency virus J Am Vet Med Assoc 196 316 318.

    • Search Google Scholar
    • Export Citation

  • 14. A.N. Patitucci M.R. Alley B.R. Jones W.A. Charleston 1997 Protozoal encephalomyelitis of dogs involving Neospora caninum and Toxoplasma gondii in New Zealand N Z Vet J 45 231 235.

    • Search Google Scholar
    • Export Citation

  • 15. S.A. Lindsay V.R. Barrs G. Child J.A. Beatty M.B. Krockenberger 2010 myelitis due to reactivated spinal toxoplasmosis in a cat J Feline Med Surg 12 818 821.

    • Search Google Scholar
    • Export Citation

  • 16. J. Flegr J. Havlícek P. Kodym M. Malý Z. Smahel 2002 Increased risk of traffic accidents in subjects with latent toxoplasmosis: a retrospective case-control study BMC Infect Dis 2 11.

    • Search Google Scholar
    • Export Citation

  • 17. K. Yereli I.C. Balcioğlu A. Ozbilgin 2006 Is Toxoplasma gondii a potential risk for traffic accidents in Turkey Forensic Sci Int 163 34 37.

    • Search Google Scholar
    • Export Citation

  • 18. T.A. Arling 2009 Toxoplasma gondii antibody titers and history of suicide attempts in patients with recurrent mood disorders J Nerv Ment Dis 197 905 908.

    • Search Google Scholar
    • Export Citation

  • 19. S. Zhu 2009 Psychosis may be associated with toxoplasmosis Med Hypotheses 73 799 801.

  • 20. D. Hinze-Selch W. Däubener S. Erdag S. Wilms 2010 The diagnosis of a personality disorder increases the likelihood for seropositivity to Toxoplasma gondii in psychiatric patients Folia Parasitol (Praha) 57 129 135.

    • Search Google Scholar
    • Export Citation

  • 21. M.G. Pedersen P.B. Mortensen B. Norgaard-Pedersen T.T. Postolache 2012 Toxoplasma gondii infection and self-directed violence in mothers Arch Gen Psychiatr 69 1123 1130.

    • Search Google Scholar
    • Export Citation

  • 22. S. Fabiani B. Pinto F. Bruschi 2013 Toxoplasmosis and neuropsychiatric diseases: can serological studies establish a clear relationship Neurol Sci 34 417 425.

    • Search Google Scholar
    • Export Citation

  • 23. J. Havlícek Z.G. Gasová A.P. Smith K. Zvára J. Flegr 2001 Decrease of psychomotor performance in subjects with latent ‘asymptomatic’ toxoplasmosis Parasitology 122 515 520.

    • Search Google Scholar
    • Export Citation

  • 24. J. Flegr 2007 Effects of toxoplasma on human behavior Schizophr Bull 33 757 760.

  • 25. M. Novotná 2008 Toxoplasma and reaction time: role of toxoplasmosis in the origin, preservation and geographical distribution of Rh blood group polymorphism Parasitology 135 1253 1261.

    • Search Google Scholar
    • Export Citation

  • 26. W.M. Hutchinson M. Bradley W.M. Cheyne B.W. Wells J. Hay 1980 Behavioural abnormalities in Toxoplasma-infected mice Ann Trop Med Parasitol 74 337 345.

    • Search Google Scholar
    • Export Citation

  • 27. J.P. Webster C.F. Brunton D.W. MacDonald 1994 Effect of Toxoplasma gondii upon neophobic behaviour in wild brown rats, Rattus norvegicus Parasitology 109 37 43.

    • Search Google Scholar
    • Export Citation

  • 28. M. Berdoy J.P. Webster D.W. MacDonald 1995 Parasite altered-behaviour: is the effect of Toxoplasma gondii on Rattus norvegicus specific Parasitology 111 403 409.

    • Search Google Scholar
    • Export Citation

  • 29. M. Berdoy J.P. Webster D.W. MacDonald 2000 Fatal attraction in rats infected with Toxoplasma gondii Proc Biol Sci 267 1591 1594.

  • 30. A. Vyas S.K. Kim N. Giacomini J.C. Boothroyd R.M. Sapolsky 2007 Behavioral changes induced by Toxoplasma infection of rodents are highly specific to aversion of cat odors Proc Natl Acad Sci USA 104 6442 6447.

    • Search Google Scholar
    • Export Citation

  • 31. M. Gulinello 2010 Acquired infection with Toxoplasma gondii in adult mice results in sensorimotor deficits but normal cognitive behavior despite widespread brain pathology Microbes Infect 12 528 537.

    • Search Google Scholar
    • Export Citation

  • 32. J. Gatkowska M. Wieczorek B. Dziadek K. Dzitko H. Dlugonska 2012 Behavioral changes in mice caused by Toxoplasma gondii invasion of brain Parasitol Res 111 53 58.

    • Search Google Scholar
    • Export Citation

  • 33. I.R. Dunay A. Fuchs L.D. Sibley 2010 Inflammatory monocytes but not neutrophils are necessary to control infection with Toxoplasma gondii in mice Infection and Immunity 78 1564 1570.

    • Search Google Scholar
    • Export Citation

  • 34. B. Hou A. Benson L. Kuzmich A.L. DeFranco F. Yarovinsky 2011 Critical coordination of innate immune defense against Toxoplasma gondii by dendritic cells responding via their Toll-like receptors Proc Natl Acad Sci USA 108 278 283.

    • Search Google Scholar
    • Export Citation

  • 35. B. John 2011 Analysis of behavior and trafficking of dendritic cells within the brain during toxoplasmic encephalitis PLoS Pathog 7 1002246.

    • Search Google Scholar
    • Export Citation

  • 36. K.R. Karlmark F. Tacke I.R. Dunay 2012 Monocytes in health and disease — Minireview Eur J Microbiol Immunol 2 97 102.

  • 37. M. Schaeffer 2009 Dynamic imaging of T cell-parasite interactions in the brains of mice chronically infected with Toxoplasma gondii J Immunol 182 6379 6393.

    • Search Google Scholar
    • Export Citation

  • 38. G. Nishanth 2010 Protective Toxoplasma gondii-specific T-cell responses require T-cell-specific expression of protein kinase C-theta Infection and Immunity 78 3454 3464.

    • Search Google Scholar
    • Export Citation

  • 39. R. Gazzinelli Y. Xu S. Hieny A. Cheever A. Sher 1992 Simultaneous depletion of CD4+ and CD8+ T lymphocytes is required to reactivate chronic infection with Toxoplasma gondii J Immunol 149 175 180.

    • Search Google Scholar
    • Export Citation

  • 40. V.B. Carruthers Y. Suzuki 2007 Effects of Toxoplasma gondii infection on the brain Schizophr Bull 33 745 751.

  • 41. C.H. Liu 2006 Cutting edge: dendritic cells are essential for in vivo IL-12 production and development of resistance against Toxoplasma gondii infection in mice J Immunol 177 31 35.

    • Search Google Scholar
    • Export Citation

  • 42. M. Mashayekhi 2011 C8α(+) dendritic cells are the critical source of interleukin-12 that controls acute infection by Toxoplasma gondii tachyzoites Immunity 35 249 259.

    • Search Google Scholar
    • Export Citation

  • 43. W. Walker C.W. Roberts D.J. Ferguson H. Jebbari J. Alexander 1997 Innate immunity to Toxoplasma gondii is influenced by gender and is associated with differences in interleukin-12 and gamma interferon production Infect Immun 65 1119 1121.

    • Search Google Scholar
    • Export Citation

  • 44. Y. Suzuki Q. Sa M. Gehman E. Ochiai 2011 Interferon-gammaand perforin-mediated immune responses for resistance against Toxoplasma gondii in the brain Expert Rev Mol Med 13 31.

    • Search Google Scholar
    • Export Citation

  • 45. D. Schlüter 2003 Both lymphotoxin-alpha and TNF are crucial for control of Toxoplasma gondii in the central nervous system J Immunol 170 6172 6182.

    • Search Google Scholar
    • Export Citation

  • 46. P.J. Gaddi G.S. Yap 2007 Cytokine regulation of immunopathology in toxoplasmosis Immunol Cell Biol 85 155 159.

  • 47. J.S. Stumhofer C.A. Hunter 2008 Advances in understanding the anti-inflammatory properties of IL-27 Immunol Lett 117 123 130.

  • 48. E.H. Wilson U. Wille-Reece F. Dzierszinski C.A. Hunter 2005 A critical role for IL-10 in limiting inflammation during toxoplasmic encephalitis J Neuroimmunol 165 63 74.

    • Search Google Scholar
    • Export Citation

  • 49. E. Prandovszky 2011 The neurotropic parasite Toxoplasma gondii increases dopamine metabolism PLoS One 6 23866.

  • 50. F. Haroon 2012 Toxoplasma gondii actively inhibits neuronal function in chronically infected mice PLoS One 7 35516.

  • 51. S. Vogler 2006 Uncoupling protein 2 has protective function during experimental autoimmune encephalomyelitis Am J Pathol 168 1570 1575.

    • Search Google Scholar
    • Export Citation

  • 52. M. Krohn 2011 Cerebral amyloid-beta proteostasis is regulated by the membrane transport protein ABCC1 in mice J Clin Invest 121 3924 3931.

    • Search Google Scholar
    • Export Citation

  • 53. K. Scheffler 2011 Determination of spatial and temporal distribution of microglia by 230-nm-high-resolution, high-throughput automated analysis reveals different amyloid plaque populations in an APP/PS1 mouse model of Alzheimer's disease Curr Alzheimer Res 8 781 788.

    • Search Google Scholar
    • Export Citation

  • 54. K. Scheffler 2012 Mitochondrial DNA polymorphisms specifically modify cerebral beta-amyloid proteostasis Acta Neuropathol 124 199 208.

    • Search Google Scholar
    • Export Citation

  • 55. T. Schumacher 2012 ABC transporters B1, C1 and G2 differentially regulate neuroregeneration in mice PLoS One 7 35613.

  • 56. C. Fröhlich 2013 Genomic background-related activation of microglia and reduced beta-amyloidosis in a mouse model of Alzheimer's disease Eur J Microbiol Immunol 3 21 27.

    • Search Google Scholar
    • Export Citation

  • 57. J. Hofrichter 2013 Reduced Alzheimer's disease pathology by St. John's Wort treatment is independent of hyperforin and facilitated by ABCC1 and microglia activation in mice Curr Alzheimer Res 10 1057 1069.

    • Search Google Scholar
    • Export Citation

  • 58. J. Pahnke C. Fröhlich M. Krohn T. Schumacher K. Paarmann 2013 Impaired mitochondrial energy production and ABC transporter function-A crucial interconnection in dementing proteopathies of the brain Mech Ageing Dev 134 506 515.

    • Search Google Scholar
    • Export Citation

  • 59. V. Bartanusz D. Jezova B. Alajajian M. Digicaylioglu 2011 The blood-spinal cord barrier: morphology and clinical implications Ann Neurol 70 194 206.

    • Search Google Scholar
    • Export Citation

  • 60. J. Neefjes M.L.M. Jongsma P. Paul O. Bakke 2011 Towards a systems understanding of MHC class I and MHC class II antigen presentation Nat Rev Immunol 11 823 836.

    • Search Google Scholar
    • Export Citation

  • 61. H.L. Wright R.J. Moots R.C. Bucknall S.W. Edwards 2010 Neutrophil function in inflammation and inflammatory diseases Rheumatology 49 1618 1631.

    • Search Google Scholar
    • Export Citation

  • 62. N.A. Prow D.N. Irani 2008 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 105 1276 1286.

    • Search Google Scholar
    • Export Citation

  • 63. E. Esposito S. Cuzzocrea 2011 Anti-TNF therapy in the injured spinal cord Trends Pharmacol Sci 32 107 115.

  • 64. M.K. Gately 1998 The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses Annu Rev Immunol 16 495 521.

    • Search Google Scholar
    • Export Citation

  • 65. M. Yaguchi S. Ohta Y. Toyama Y. Kawakami M. Toda 2008 Functional recovery after spinal cord injury in mice through activation of microglia and dendritic cells after IL-12 administration J Neurosci Res 86 1972 1980.

    • Search Google Scholar
    • Export Citation

  • 66. R. Vasconcellos N.A. Carter E.C. Rosser C. Mauri 2011 IL-12p35 subunit contributes to autoimmunity by limiting IL-27-driven regulatory responses J Immunol 187 3402 3412.

    • Search Google Scholar
    • Export Citation

  • 67. R. Li 2012 Gene silencing of IL-12 in dendritic cells inhibits autoimmune arthritis J Transl Med 10 19.

  • Collapse
  • Expand
Cover European Journal of Microbiology and Immunology
European Journal of Microbiology and Immunology
Print ISSN:
2062-509X
Online ISSN:
2062-8633

Senior editors

Editor(s)-in-Chief: Dunay, Ildiko Rita, Prof. Dr. Pharm, Dr. rer. nat., University of Magdeburg, Germany

Editor(s)-in-Chief: Heimesaat, Markus M., Prof. Dr. med., Charité - University Medicine Berlin, Germany

Editorial Board

  • Berit Bangoura, Dr. DVM. PhD,  University of Wyoming, USA
  • Stefan Bereswill, Prof. Dr. rer. nat., Charité - University Medicine Berlin, Germany
  • Dunja Bruder, Prof. Dr. rer. nat., University of Magdeburg, Germany
  • Jan Buer, Prof. Dr. med., University of Duisburg, Germany
  • Edit Buzas, Prof. Dr. med., Semmelweis University, Hungary
  • Renato Damatta, Prof. PhD, UENF, Brazil
  • Maria Deli, MD, PhD, DSc, Biological Research Center, HAS, Hungary
  • Olgica Djurković-Djaković, Prof. Phd, University of Belgrade, Serbia
  • Jean-Dennis Docquier, Prof. Dr. med., University of Siena, Italy
  • Zsuzsanna Fabry, Prof. Phd, University of Washington, USA
  • Ralf Ignatius, Prof. Dr. med., Charité - University Medicine Berlin, Germany
  • Achim Kaasch, Prof. Dr. med., Otto von Guericke University Magdeburg, Germany
  • Oliver Liesenfeld, Prof. Dr. med., Inflammatix, USA
  • Matyas Sandor, Prof. PhD, University of Wisconsin, USA
  • Ulrich Steinhoff, Prof. PhD, University of Marburg, Germany
  • Michal Toborek, Prof. PhD, University of Miami, USA
  • Susanne A. Wolf, PhD, MDC-Berlin, Germany

 

Dr. Dunay, Ildiko Rita
Magdeburg, Germany
E-mail: ildiko.dunay@med.ovgu.de

Indexing and Abstracting Services:

  • PubMed Central
  • Scopus
  • ESCI
  • CABI
  • CABELLS Journalytics

 

2024  
Scopus  
CiteScore  
CiteScore rank  
SNIP  
Scimago  
SJR index 0.569
SJR Q rank Q3

2023  
Web of Science  
Total Cites
WoS		 674
Journal Impact Factor 3.3
Rank by Impact Factor

Q2
Impact Factor
without
Journal Self Cites		 3.1
5 Year
Impact Factor		 3.2
Scimago  
Scimago
H-index		 15
Scimago
Journal Rank		 0.601
Scimago Quartile Score Microbiology (medical) (Q2)
Microbiology (Q3)
Immunology and Allergy (Q3)
Immunology (Q3)
Scopus  
Scopus
Cite Score		 5.0
Scopus
CIte Score Rank		 Microbiology (medical) Q2
Scopus
SNIP		 0.832

 

European Journal of Microbiology and Immunology
Publication Model Gold Open Access
Online only
Submission Fee none
Article Processing Charge 900 EUR/article
Regional discounts on country of the funding agency World Bank Lower-middle-income economies: 50%
World Bank Low-income economies: 100%
Further Discounts Editorial Board / Advisory Board members: 50%
Corresponding authors, affiliated to an EISZ member institution subscribing to the journal package of Akadémiai Kiadó: 100%
Subscription Information Gold Open Access
Purchase per Title  

European Journal of Microbiology and Immunology
Language English
Size A4
Year of
Foundation		 2011
Volumes
per Year		 1
Issues
per Year		 4
Founder Akadémiai Kiadó
Founder's
Address		 H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Publisher Akadémiai Kiadó
Publisher's
Address		 H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher		 Chief Executive Officer, Akadémiai Kiadó
ISSN 2062-509X (Print)
ISSN 2062-8633 (Online)

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Dec 2024 38 0 0
Jan 2025 41 0 0
Feb 2025 77 0 0
Mar 2025 108 1 0
Apr 2025 45 0 0
May 2025 7 0 0
Jun 2025 0 0 0