Expression and Functionality Study of 9 Toll-Like Receptors in 33 Drug-Naïve Non-Affective First Episode Psychosis Individuals: A 3-Month Study

Int J Mol Sci. 2020 Aug 25;21(17):6106. doi: 10.3390/ijms21176106.

Abstract

Toll-like receptors (TLRs) are a pivotal component of the innate immune system that seem to have a role in the pathogenesis of psychosis. The purpose of this work was to compare the expression and functionality of 9 TLRs in three peripheral blood mononuclear cells (PBMCs) (monocytes, B cells, and T cells) between 33 drug-naïve first-episode psychosis (FEP) individuals and 26 healthy volunteers, at baseline and after 3-month of antipsychotic treatment. The expression of TLRs 1-9 were assessed by flow cytometry. For the assessment of the TLR functionality, cells collected in sodium heparin tubes were polyclonally stimulated for 18 h, with different agonists for human TLR1-9. The results of our study highlight the role that TLR5 and TLR8 might play in the pathophysiology of psychosis. We found a lower expression of these receptors in FEP individuals, regarding healthy volunteers at baseline and after 3-month of treatment on the three PBMCs subsets. Most TLRs showed a lower functionality (especially reduced intracellular levels of TNF-α) in patients than in healthy volunteers. These results, together with previous evidence, suggest that individuals with psychosis might show a pattern of TLR expression that differs from that of healthy volunteers, which could vary according to the intensity of immune/inflammatory response.

Keywords: cytokines; neuroinflammation; psychosis; toll-like receptors.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use
  • B-Lymphocytes / metabolism
  • Case-Control Studies
  • Female
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Prospective Studies
  • Psychotic Disorders / drug therapy
  • Psychotic Disorders / metabolism*
  • T-Lymphocytes / metabolism
  • Toll-Like Receptor 5 / metabolism*
  • Toll-Like Receptor 8 / metabolism*
  • Young Adult

Substances

  • Antipsychotic Agents
  • TLR5 protein, human
  • TLR8 protein, human
  • Toll-Like Receptor 5
  • Toll-Like Receptor 8