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Immunomodulation of Mature Dendritic Cells in Parkinson's Disease: A Novel Role of Intracellular Toll Like Receptors
Author(s) -
Paterniti Irene,
Campolo Michela,
Cordaro Marika,
Casili Giovanna,
Lanza Marika,
Filippone Alessia,
Esposito Emanuela,
Cuzzocrea Salvatore
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.500.19
Subject(s) - neuroinflammation , microglia , immune system , innate immune system , biology , receptor , immunology , toll like receptor , cytokine , microbiology and biotechnology , neuroscience , inflammation , biochemistry
Parkinson's disease (PD) is a devastating clinical disorders that is characterized by progressive and selective neuronal injury and cell death. Recent studies have provided accumulating evidence for a significant role of the immune system and neuroinflammation in PD pathogenesis. In particular, neuroinflammation associated to PD is the prerequisite for the maturation of dendritic cells (DC) and their migration to the respective sites in the brain. It has become clear that Toll‐like receptors (TLRs), a major family of pattern recognition receptors could mediate innate and adaptive immune response, providing an important mechanism by which microglia are able to sense both pathogen‐ and host derived ligands within the CNS. The aim of our study was to evaluate the role of TLR 7,8 and 9 in DC maturation that trigger to adaptive autoimmune response related to PD. We performed an in vivo model of PD, by MPTP, in single KO mice for TLR7 − , TLR8 − and TLR9 − ; and in double KO mice for TLR 7/8 −/− and TLR7/9 −/− . All animals was compared with WT animals used as a control group. Animals were sacrificed after 8 days and their midbrains were harvested, sectioned and processed in order to evaluate: the principal markers of PD with particular attention to TH, DAT and α‐synuclein aggregate; astrocytes and microglia activation through GFAP and IBA‐1; pro‐inflammatory cytokine's expression such as INF‐γ and TNF‐α like major product of activated microglia and astrocytes. Moreover to evaluate the formation of neuromelanin pigments in the midbrain we made the Masson‐Fontana staining. The result obtained demonstrated that the genetic absence of TLR 7,8 and 9 modified PD pathway increasing significantly the immunoreactivity for TH and DAT compared to PD groups where we found an evident reduction of these markers. Therefore, TLRs could be considered as a possible target to develop new therapies for neurodegenerative disorders. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .