A novel mouse model to show that a fatal central nervous system (CNS) disease can be caused by a pathogen that does not replicate in the CNS has been developed by a research team led by Glenn Rall at the Fox Chase Cancer Center in Philadelphia, PA.
The results of this new study are published December 22nd in the Open Access journal PLoS Pathogens.
The authors found that the immune response induced in response to a peripheral viral infection can be "mis-recruited" to the brain, where these activated immune cells can then lead to inflammation-induced neuropathology and disease. While "mis-recruitment" has been observed in other mouse models, this is the first study to show that this phenomenon can have pathogenic consequences.
While the broader implications of this study await further investigation, this is a proof of principle study that addresses a key question: can a pathogen cause disease "at a distance"? Typically, we envision that diseases are manifested where infectious pathogens replicate: influenza causes respiratory infection because this is the primary site of replication. In contrast, this study suggests that infection can activate immune responses that can be deleterious in tissues that are not directly infected by the initiating pathogen. This may be of broader relevance to human CNS diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis.
The authors of this study point out, however, that "while making direct connections between this model system and human diseases would be premature, a similar phenomenon could account for both the reported increase in inflammatory cells found in the brain of patients, as well as the lack of consistent and convincing presence of any specific pathogen in the brains of affected individuals."