Activated Immune Cells in Parkinson's Disease

Abstract

Recently, an interaction between neurodegenerative processes and the innate and adaptive immune responses has been increasingly recognized. Activation of microglia, infiltration of peripheral T lymphocytes, and T-cell interaction with microglia may strongly affect the progression of Parkinson's disease (PD) both in patients and in animal models of the disease. Here, we summarize the current knowledge regarding the role of microglia in the progression of PD. The plasticity of the microglial response is also discussed in the context of PD. In addition, we also focus on the influence of several peripheral T-cell subsets on PD progression as well as on possible pathways by which they might act. This review should help increase our understanding of the effects of innate and adaptive immune cells in the pathogenesis of PD.

Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease

“…These studies implicate that the adaptive immune system contributes to the progression and pathogenesis of PD (extensively reviewed by (Cao et al, 2011) and indicate that this promising line of investigation (which will be further discussed below as a potential immunomodulatory therapy) warrants additional work to determine definitive targets for PD therapies.…”

“…In a more recent study, the adaptive immune response and nigrostriatal dopaminergic neurodegeneration generated as a result of immunization of MPTP-treated mice with nitrated -synuclein was attenuated by VIP-induced Tregs (Reynolds et al, 2010). This effect was mediated in part through Tregs suppression of Th17-mediated inflammatory response and the mechanism has been proposed as a potential immunisation strategy for PD (Cao et al, 2011;Reynolds et al, 2010). Thus manipulating this adaptive response by redirecting the harmful T-cell response towards an anti-inflammatory and protective immune response by means of an antigen-based immunisation could be a successful approach for neuroprotection in PD.…”

“…Since then an abundance of clinical and animal studies supports the role of activated microglia and increased levels of inflammatory mediators such as cytokines, chemokines and ROS in the pathology of PD (Banati et al, 1998;Barcia et al, 2011;Boka et al, 1994;Cao et al, 2011;Crotty et al, 2008;Depino et al, 2003;Dobbs et al, 1999;Hirsch and Hunot, 2009;Imamura et al, 2003;Long-Smith et al, 2010;Long-Smith et al, 2009;McGeer and McGeer, 2004;Mogi et al, 1994a, b;Mount et al, 2007;Orr et al, 2002;Tansey et al, 2007). Enzymes associated with inflammation, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), have also been identified post-mortem in PD brains (Hunot et al, 1996;Knott et al, 2000).…”

Role of microglia in CNS inflammation

“…On the other hand, the adaptive immune responses, most notably T cells, are now emerging as important components of the inflammatory response that contributes to the pathogenesis of PD.'' Other authors suggest that activated microglia are widely considered to participate in the progression of PD [29] and advocate a role for the immune system in PD [30]. In PD animal models caused by intoxicating mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the cellular reaction includes MHC class I and II positive microglia, reactive astrocytes and T cells that infiltrate the substantia nigra and striatum and gather in the meninges [31].…”

Inflammatory Regulation of ATP Binding Cassette Efflux Transporter Expression and Function in Microglia

“…In adult animals, microglia are generally present in a stationary, ramified state and continuously monitor the neural parenchyma through finger-like cytoplasmic projections. Microglia can be stimulated by infections, cerebral ischemia, traumatic brain injury, or neuronal/parenchymal damage to remove necrotic and apoptotic debris and coordinate immune responses (Rogers et al, 2007;Badoer, 2010;Cao et al, 2011a). Activated microglia progressively increase in number during the normal aging process and are also commonly present in neurodegenerative diseases.…”