1887

Abstract

Microglial activation is a hallmark of the neuroimmunological response to Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and prion disease. The CX3C chemokine axis consists of fractalkine (CX3CL1) and its receptor (CX3CR1); these are expressed by neurons and microglia respectively, and are known to modulate microglial activation. In prion-infected mice, both Cx3cr1 and Cx3cl1 are altered, suggesting a role in disease. To investigate the influence of CX3C axis signalling on prion disease, we infected Cx3cr1 knockout (Cx3cr1-KO) and control mice with scrapie strains 22L and RML. Deletion of Cx3cr1 had no effect on development of clinical signs or disease incubation period. In addition, comparison of brain tissue from Cx3cr1-KO and control mice revealed no significant differences in cytokine levels, spongiosis, deposition of disease-associated prion protein or microglial activation. Thus, microglial activation during prion infection did not require CX3C axis signalling.

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2016-06-28
2019-10-19
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References

  1. Aguzzi A., Nuvolone M., Zhu C..( 2013;). The immunobiology of prion diseases. . Nat Rev Immunol13:888–902. [CrossRef][PubMed]
    [Google Scholar]
  2. Biber K., Neumann H., Inoue K., Boddeke H. W..( 2007;). Neuronal ‘On' and ‘Off' signals control microglia. . Trends Neurosci30:596–602. [CrossRef][PubMed]
    [Google Scholar]
  3. Biber K., Owens T., Boddeke E..( 2014;). What is microglia neurotoxicity (Not)?. Glia62:841–854. [CrossRef][PubMed]
    [Google Scholar]
  4. Cardona A. E., Pioro E. P., Sasse M. E., Kostenko V., Cardona S. M., Dijkstra I. M., Huang D., Kidd G., Dombrowski S., Ransohoff R. M..( 2006;). Control of microglial neurotoxicity by the fractalkine receptor. . Nat Neurosci9:917–924. [CrossRef][PubMed]
    [Google Scholar]
  5. Cho S. H., Sun B., Zhou Y., Kauppinen T. M., Halabisky B., Wes P., Ransohoff R. M., Gan L..( 2011;). CX3CR1 protein signaling modulates microglial activation and protects against plaque-independent cognitive deficits in a mouse model of Alzheimer disease. . J Biol Chem286:32713–32722. [CrossRef][PubMed]
    [Google Scholar]
  6. Combadière C., Potteaux S., Gao J. L., Esposito B., Casanova S., Lee E. J., Debré P., Tedgui A., Murphy P. M., Mallat Z..( 2003;). Decreased atherosclerotic lesion formation in CX3CR1/apolipoprotein E double knockout mice. . Circulation107:1009–1016. [CrossRef][PubMed]
    [Google Scholar]
  7. Cunningham C., Deacon R., Wells H., Boche D., Waters S., Diniz C. P., Scott H., Rawlins J. N., Perry V. H..( 2003;). Synaptic changes characterize early behavioural signs in the ME7 model of murine prion disease. . Eur J Neurosci17:2147–2155. [CrossRef][PubMed]
    [Google Scholar]
  8. Grizenkova J., Akhtar S., Brandner S., Collinge J., Lloyd S. E..( 2014;). Microglial Cx3cr1 knockout reduces prion disease incubation time in mice. . BMC Neurosci15:44. [CrossRef][PubMed]
    [Google Scholar]
  9. Hughes P. M., Botham M. S., Frentzel S., Mir A., Perry V. H..( 2002;). Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, during acute and chronic inflammation in the rodent CNS. . Glia37:314–327. [CrossRef][PubMed]
    [Google Scholar]
  10. Jung S., Aliberti J., Graemmel P., Sunshine M. J., Kreutzberg G. W., Sher A., Littman D. R..( 2000;). Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. . Mol Cell Biol20:4106–4114. [CrossRef][PubMed]
    [Google Scholar]
  11. Kostadinova F. I., Baba T., Ishida Y., Kondo T., Popivanova B. K., Mukaida N..( 2010;). Crucial involvement of the CX3CR1-CX3CL1 axis in dextran sulfate sodium-mediated acute colitis in mice. . J Leukoc Biol88:133–143. [CrossRef][PubMed]
    [Google Scholar]
  12. Lee S., Varvel N. H., Konerth M. E., Xu G., Cardona A. E., Ransohoff R. M., Lamb B. T..( 2010;). CX3CR1 deficiency alters microglial activation and reduces beta-amyloid deposition in two Alzheimer’s disease mouse models. . Am J Pathol177:2549–2562. [CrossRef][PubMed]
    [Google Scholar]
  13. Limatola C., Ransohoff R. M..( 2014;). Modulating neurotoxicity through CX3CL1/CX3CR1 signaling. . Front Cell Neurosci8:229. [CrossRef][PubMed]
    [Google Scholar]
  14. Medina-Contreras O., Geem D., Laur O., Williams I. R., Lira S. A., Nusrat A., Parkos C. A., Denning T. L..( 2011;). CX3CR1 regulates intestinal macrophage homeostasis, bacterial translocation, and colitogenic Th17 responses in mice. . J Clin Invest121:4787–4795. [CrossRef][PubMed]
    [Google Scholar]
  15. Paolicelli R. C., Bisht K., Tremblay M. È..( 2014;). Fractalkine regulation of microglial physiology and consequences on the brain and behavior. . Front Cell Neurosci8:129. [CrossRef][PubMed]
    [Google Scholar]
  16. Park K. W., Lee H. G., Jin B. K., Lee Y. B..( 2007;). Interleukin-10 endogenously expressed in microglia prevents lipopolysaccharide-induced neurodegeneration in the rat cerebral cortex in vivo. . Exp Mol Med39:812–819. [CrossRef][PubMed]
    [Google Scholar]
  17. Prinz M., Priller J., Sisodia S. S., Ransohoff R. M..( 2011;). Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. . Nat Neurosci14:1227–1235. [CrossRef][PubMed]
    [Google Scholar]
  18. Rangel A., Race B., Phillips K., Striebel J., Kurtz N., Chesebro B..( 2014;). Distinct patterns of spread of prion infection in brains of mice expressing anchorless or anchored forms of prion protein. . Acta Neuropathol Commun2:8. [CrossRef][PubMed]
    [Google Scholar]
  19. Ransohoff R. M., Schafer D., Vincent A., Blachère N. E., Bar-Or A..( 2015;). Neuroinflammation: ways in which the immune system affects the brain. . Neurotherapeutics12:896–909. [CrossRef][PubMed]
    [Google Scholar]
  20. Saijo K., Glass C. K..( 2011;). Microglial cell origin and phenotypes in health and disease. . Nat Rev Immunol11:775–787. [CrossRef][PubMed]
    [Google Scholar]
  21. Smith J. A., Das A., Ray S. K., Banik N. L..( 2012;). Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. . Brain Res Bull87:10–20. [CrossRef][PubMed]
    [Google Scholar]
  22. Song C. H., Honmou O., Furuoka H., Horiuchi M..( 2011;). Identification of chemoattractive factors involved in the migration of bone marrow-derived mesenchymal stem cells to brain lesions caused by prions. . J Virol85:11069–11078. [CrossRef][PubMed]
    [Google Scholar]
  23. Striebel J. F., Race B., Meade-White K. D., LaCasse R., Chesebro B..( 2011;). Strain specific resistance to murine scrapie associated with a naturally occurring human prion protein polymorphism at residue 171. . PLoS Pathog7:e1002275. [CrossRef][PubMed]
    [Google Scholar]
  24. Tamgüney G., Giles K., Glidden D. V., Lessard P., Wille H., Tremblay P., Groth D. F., Yehiely F., Korth C., Prusiner S. B..( 2008;). Genes contributing to prion pathogenesis. . J Gen Virol89:1777–1788. [CrossRef][PubMed]
    [Google Scholar]
  25. Tribouillard-Tanvier D., Race B., Striebel J. F., Carroll J. A., Phillips K., Chesebro B..( 2012;). Early cytokine elevation, PrPres deposition, and gliosis in mouse scrapie: no effect on disease by deletion of cytokine genes IL-12p40 and IL-12p35. . J Virol86:10377–10383. [CrossRef][PubMed]
    [Google Scholar]
  26. Ullman-Culleré M. H., Foltz C. J..( 1999;). Body condition scoring: a rapid and accurate method for assessing health status in mice. . Lab Anim Sci49:319–323.[PubMed]
    [Google Scholar]
  27. Wolf Y., Yona S., Kim K. W., Jung S..( 2013;). Microglia, seen from the CX3CR1 angle. . Front Cell Neurosci7:26. [CrossRef][PubMed]
    [Google Scholar]
  28. Xie W. L., Shi Q., Zhang J., Zhang B. Y., Gong H. S., Guo Y., Wang S. B., Xu Y., Wang K., Dong X. P..( 2013;). Abnormal activation of microglia accompanied with disrupted CX3CR1/CX3CL1 pathway in the brains of the hamsters infected with scrapie agent 263K. . J Mol Neurosci51:919–932. [CrossRef][PubMed]
    [Google Scholar]
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