CNS cell-type localization and LPS response of TLR signaling pathways.

Autor:	McCarthy GM; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, 78712, USA.; Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX, 78712, USA., Bridges CR; Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX, 78712, USA., Blednov YA; Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX, 78712, USA., Harris RA; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, 78712, USA.; Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX, 78712, USA.; Insitute for Neuroscience, University of Texas at Austin, Austin, TX, 78712, USA.
Jazyk:	angličtina
Zdroj:	F1000Research [F1000Res] 2017 Jul 19; Vol. 6, pp. 1144. Date of Electronic Publication: 2017 Jul 19 (Print Publication: 2017).
DOI:	10.12688/f1000research.12036.1
Abstrakt:	Background: Innate immune signaling in the brain has emerged as a contributor to many central nervous system (CNS) pathologies, including mood disorders, neurodegenerative disorders, neurodevelopmental disorders, and addiction. Toll-like receptors (TLRs), a key component of the innate immune response, are particularly implicated in neuroimmune dysfunction. However, most of our understanding about TLR signaling comes from the peripheral immune response, and it is becoming clear that the CNS immune response is unique. One controversial aspect of neuroimmune signaling is which CNS cell types are involved. While microglia are the CNS cell-type derived from a myeloid lineage, studies suggest that other glial cell types and even neurons express TLRs, although this idea is controversial. Furthermore, recent work suggests a discrepancy between RNA and protein expression within the CNS. Methods: To elucidate the CNS cell-type localization of TLRs and their downstream signaling molecules, we isolated microglia and astrocytes from the brain of adult mice treated with saline or the TLR4 ligand lipopolysaccharide (LPS). Glial mRNA and protein expression was compared to a cellular-admixture to determine cell-type enrichment. Results: Enrichment analysis revealed that most of the TLR pathway genes are localized in microglia and changed in microglia following immune challenge. However, expression of Tlr3 was enriched in astrocytes, where it increased in response to LPS. Furthermore, attempts to determine protein cell-type localization revealed that many antibodies are non-specific and that antibody differences are contributing to conflicting localization results. Conclusions: Together these results highlight the cell types that should be looked at when studying TLR signaling gene expression and suggest that non-antibody approaches need to be used to accurately evaluate protein expression. Competing Interests: Competing interests: No competing interests were disclosed.
Databáze:	MEDLINE
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