Analysis of Toll-Like Receptor-2 and 4 Expressions in Peripheral Monocyte Subsets in Patients with Type 1 Diabetes Mellitus

Immunol Invest. 2021 Feb;50(2-3):113-124. doi: 10.1080/08820139.2020.1714649. Epub 2020 Apr 13.


Background: Dysfunction of the peripheral blood monocytes in the form of changes in their proportion, cytokines or pattern-recognition receptors (PRR) expressions may be involved in the pathogenesis of type 1 diabetes mellitus (T1DM). Our aim is to analyze the three monocyte subsets; classical, non-classical and intermediate monocytes and their expression of Toll-like receptors 2 (TLR-2) and 4 (TLR-4) in T1DM patients. Methods: The peripheral blood monocytes of 20 T1DM patients were analyzed by Flow cytometry to measure their count and TLR-2 and TLR-4 expression. Results: T1DM patients had more non-classical and intermediate monocytes, whereas classical monocytes were comparable between patients and control (20 healthy volunteers). Classical, non-classical and intermediate monocytes had no significant correlations with hemoglobin (Hb) A1C in controls, while all subsets showed positive correlations with HbA1C in T1DM. TLR-2 and TLR-4 expression were significantly increased in classical monocytes in patients, especially those with diabetic ketoacidosis (DKA), and both of them showed positive correlations with the duration of T1DM. The expression of TLR-2 inside non-classical monocytes showed a negative correlation with LDL cholesterol and TLR-4/TLR-2 ratio showed positive correlations with the duration of T1DM and negative correlations with total cholesterol. The expression of TLR-2 inside intermediate monocytes showed positive correlations with the duration of T1DM and TLR-4/TLR-2 ratio showed negative correlations with the duration of T1DM Conclusions: The observed changes in both proportions and TLR-2 and TLR-4 expression of monocyte subsets can raise the possible role in the pathogenesis of early stages of T1DM and DKA. Abbreviations APC: allophycocyanin; CBC: complete blood picture; DKA: diabetic acidosis; DM: diabetes mellitus; FITC: fluorescein isothiocyanate; FSC: forward scatter; Hb: haemoglobin; MFI: mean channel fluorescence intensity; PE: phycoerythrin; PRR: pattern-recognition receptors; SPSS: statistical package for the social sciences; SSC: side scatter; T1DM: Type1DM; TLRs: toll-like receptors.

Keywords: FACS analysis; monocytes; toll-like receptor-2; toll-like receptor-4; type 1 diabetes.

MeSH terms

  • Cell Separation
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetic Ketoacidosis / immunology*
  • Disease Progression
  • Female
  • Flow Cytometry
  • Glycated Hemoglobin / metabolism
  • Humans
  • Male
  • Monocytes / physiology*
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*


  • Glycated Hemoglobin A
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4