TOLL-LIKE RECEPTOR-MEDIATED FUNCTIONAL ACTIVITY OF MONONUCLEAR CELLS IN CHILDREN WITH NEUTROPENIA

Aim. To study the Toll-like receptor (TLR)- mediated functional activity of peripheral blood mononuclear cells (PBMC) from children with different forms of neutropenia. Materials and methods. TLR-mediated functional activity of PBMC was evaluated by production of proinflammatory cytokines — TNFα and IFNα. Ligands for TLR1/2,TLR 2/6, TLR4, TLR5, and TLR9 were used to stimulate TNFα production by PBMC from healthy children and children with neutropenia. Ligands for TLR3, TLR4, TLR7, TLR7/8, TLR8, and TLR9 were used to induce production of IFNα. Levels of TNFα and IFNα were measured in PBMC supernatants by ELISA. The group of patients with neutropenia included 9 children with immune neutropenia and 3 children with congenital neutropenia. Control group consisted of 12 healthy children of the same age range. Results. It was revealed that TLR2, TLR4, and TLR5 ligands have enhanced stimulating effect on TNFα production by PBMC of children with congenital neutropenia and had no effect on PBMC of children with immune neutropenia. Children with immune neutropenia are characterized by significantly increased IFNα production induced by ligands of TLR3, TLR8, and TLR9. Conclusion. Revealed changes of TLR-mediated functional activity of PBMC from children with various forms of neutropenia may play significant role in development and course of infections in these patients.

Toll-like receptors, neutropenia, TNFα, IFNα