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Review
. 2009 Dec;4(4):462-75.
doi: 10.1007/s11481-009-9166-2. Epub 2009 Aug 11.

CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease?

Kavon Rezai-Zadeh  1 , David Gate, Terrence Town
Affiliations
Review

CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease?

Kavon Rezai-Zadeh et al. J Neuroimmune Pharmacol. 2009 Dec.

Abstract

While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as "immune privilege," it is now clear that immune responses do occur in the CNS-giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue.

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Figures

Fig. 1
Fig. 1
Confocal microscopy reveals activated microglia (green signal) clustered around Aβ deposits (magenta signal) in an 18-month-old Tg2576 mouse model of AD. Reproduced from Town et al. (2008)
Fig. 2
Fig. 2
Confocal microscopy showing vascular Aβ deposits (green signal) and infiltrating blood-borne macrophages (red signal) in an 18-month-old Tg2576 AD mouse model deficient in TGF-β-Smad 2/3 innate immune signaling. Reproduced from Town et al. (2008)
Fig. 3
Fig. 3
a Confocal image of a wild-type C57BL/6 mouse brain 6 days after WNV infection. Green signal indicates infiltrating leukocytes, red signal shows WNV-infected brain cells, and blue signal shows DAPI cell nuclei. b Brain flow cytometry results 6 days after WNV infection of wild-type vs. Tlr7-deficient mice. Note the reduction in brain-infiltrating immune cell subsets in Tlr7-deficient mice. Reproduced from Town et al. (2009) with permission from Cell Press
Fig. 4
Fig. 4
Model for detrimental versus beneficial roles of CNS immune cell traffic. See text for references
See this image and copyright information in PMC

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