This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baker, C. A. Articles by Manuelidis, L. Search for Related Content PubMed PubMed Citation Articles by Baker, C. A. Articles by Manuelidis, L.

Microglia from Creutzfeldt-Jakob Disease-Infected Brains Are Infectious and Show Specific mRNA Activation Profiles

Section of Neuropathology, Yale University School of Medicine, New Haven, Connecticut 06510

Received 25 February 2002/ Accepted 16 July 2002

Neurons are often assumed to be the principal sites for replication of the infectious agents causing Creutzfeldt-Jakob disease (CJD), scrapie, and bovine spongiform encephalopathy because they express high levels of normal and pathological prion protein (PrP). However, isolated brain cell types have not been evaluated for either infection or gene expression. Microglia purified from CJD-infected mice showed infectivity comparable to that of starting brain homogenate but expressed 50-fold less PrP. CJD-infected microglia also displayed morphological changes indicative of cellular activation. To determine the molecular pathways of activation, we evaluated pertinent transcripts, including those linked to inflammation. Semiquantitative reverse transcription-PCR showed a >4-fold increase in cathepsin S, an enzyme important in antigen presentation, the cytokine interleukin-1ß, and the chemokine B-lymphocyte chemoattractant. The profile of microglial changes induced by the CJD agent differed substantially from activation induced by bacterial lipopolysaccharide or by ß-amyloid, a structure comparable to pathological PrP. These microglial studies emphasize migratory hematopoietic cells in the dispersion, and possibly replication, of the CJD agent. The low PrP levels in these highly infectious and activated cells further support the concept that pathological PrP is the result of infection rather than the infectious agent itself. Because microglia develop a specific pattern of responses to the CJD agent, microglial markers may be exploited in the diagnosis of these spongiform encephalopathies.

This article has been cited by other articles:

• Kercher, L., Favara, C., Striebel, J. F., LaCasse, R., Chesebro, B. (2007). Prion Protein Expression Differences in Microglia and Astroglia Influence Scrapie-Induced Neurodegeneration in the Retina and Brain of Transgenic Mice. J. Virol. 81: 10340-10351 [Abstract] [Full Text]  
• Manuelidis, L., Yu, Z.-X., Barquero, N., Mullins, B. (2007). Cells infected with scrapie and Creutzfeldt-Jakob disease agents produce intracellular 25-nm virus-like particles. Proc. Natl. Acad. Sci. USA 104: 1965-1970 [Abstract] [Full Text]  
• Iwamaru, Y., Takenouchi, T., Ogihara, K., Hoshino, M., Takata, M., Imamura, M., Tagawa, Y., Hayashi-Kato, H., Ushiki-Kaku, Y., Shimizu, Y., Okada, H., Shinagawa, M., Kitani, H., Yokoyama, T. (2007). Microglial Cell Line Established from Prion Protein-Overexpressing Mice Is Susceptible to Various Murine Prion Strains. J. Virol. 81: 1524-1527 [Abstract] [Full Text]  
• Priller, J., Prinz, M., Heikenwalder, M., Zeller, N., Schwarz, P., Heppner, F. L., Aguzzi, A. (2006). Early and Rapid Engraftment of Bone Marrow-Derived Microglia in Scrapie.. J. Neurosci. 26: 11753-11762 [Abstract] [Full Text]  
• Stoeck, K., Bodemer, M., Ciesielczyk, B., Meissner, B., Bartl, M., Heinemann, U., Zerr, I. (2005). Interleukin 4 and Interleukin 10 Levels Are Elevated in the Cerebrospinal Fluid of Patients With Creutzfeldt-Jakob Disease. Arch Neurol 62: 1591-1594 [Abstract] [Full Text]  
• Marella, M., Gaggioli, C., Batoz, M., Deckert, M., Tartare-Deckert, S., Chabry, J. (2005). Pathological Prion Protein Exposure Switches on Neuronal Mitogen-activated Protein Kinase Pathway Resulting in Microglia Recruitment. J. Biol. Chem. 280: 1529-1534 [Abstract] [Full Text]  
• Thackray, A. M., McKenzie, A. N., Klein, M. A., Lauder, A., Bujdoso, R. (2004). Accelerated Prion Disease in the Absence of Interleukin-10. J. Virol. 78: 13697-13707 [Abstract] [Full Text]  
• Viguie, C, Chilliard, Y, Gayrard, V, Picard-Hagen, N, Monget, P, Dutour, A, Toutain, P-L (2004). Alterations of somatotropic function in prion disease in sheep. J Endocrinol 183: 427-435 [Abstract] [Full Text]  
• Rock, R. B., Gekker, G., Hu, S., Sheng, W. S., Cheeran, M., Lokensgard, J. R., Peterson, P. K. (2004). Role of Microglia in Central Nervous System Infections. Clin. Microbiol. Rev. 17: 942-964 [Abstract] [Full Text]  
• Cronier, S., Laude, H., Peyrin, J.-M. (2004). Prions can infect primary cultured neurons and astrocytes and promote neuronal cell death. Proc. Natl. Acad. Sci. USA 101: 12271-12276 [Abstract] [Full Text]  
• Golden, J. W., Bahe, J. A., Lucas, W. T., Nibert, M. L., Schiff, L. A. (2004). Cathepsin S Supports Acid-independent Infection by Some Reoviruses. J. Biol. Chem. 279: 8547-8557 [Abstract] [Full Text]  
• Mallucci, G., Dickinson, A., Linehan, J., Klohn, P.-C., Brandner, S., Collinge, J. (2003). Depleting Neuronal PrP in Prion Infection Prevents Disease and Reverses Spongiosis. Science 302: 871-874 [Abstract] [Full Text]  
• Manuelidis, L., Lu, Z. Y. (2003). Virus-like interference in the latency and prevention of Creutzfeldt-Jakob disease. Proc. Natl. Acad. Sci. USA 100: 5360-5365 [Abstract] [Full Text]  
• Baker, C. A., Manuelidis, L. (2003). Unique inflammatory RNA profiles of microglia in Creutzfeldt-Jakob disease. Proc. Natl. Acad. Sci. USA 100: 675-679 [Abstract] [Full Text]