Expression and functionality study of 9 Toll-like receptors in drug-naïve non-affective first episode psychosis individuals: a 3-month study

Abstract

Background: Toll-like receptors (TLRs) are a pivotal component of the innate immune system, which are expressed by various subsets of immune cell types, included central nervous system. There are few publications that have studied TLR expression and/or functionality in psychosis, of which most of them have been based on chronic schizophrenia individuals.Objectives: To compare the expression and functionality of 9TLRs in three peripheral blood mononuclear cells (PBMCs) (monocytes, B cells and T cells) within a sample of 33 drug-naïve FEP individuals and 26 healthy volunteers, at baseline and after 3-month of antipsychotic treatment.Methods: The expression of TLR1-9 was assessed by flow cytometry. For the assessment of the TLR functionality (measured as intracellular production of IL-1β, IL-6 and TNF-α following TLR stimulation), cells collected in sodium heparin tubes were polyclonally stimulated for 18h with different agonists for human TLR1–9.Results: Patients showed a lower expression of TLR5 and TLR8 on the three PBMCs at baseline and after 3-month of treatment regarding healthy volunteers (all ps <0.01). We also found less production of some intracellular pro-inflammatory cytokines (especially TNF-α) after TLR stimulation in patients at both baseline and following the medication (all ps <0.01). We have not found differences in the intra-subject analyses after 3-month of treatment.Conclusions: Drug-naive patients with schizophrenia spectrum disorders show lower expression of specific TLR receptors as well as lower intracellular concentrations of some pro-inflammatory cytokines after TLR stimulation. These findings may be a consequence of an excessive cell stimulation via exogenous ligands (such as pathogens) and/or endogenous ligands (such as autoimmunity) in such a way that PBMCs could be exhausted to be activated in the in vitro analyses.