[Toll-like receptor-mediated functional activity of mononuclear cells in children with neutropenia].
L V Koval'chuk, Khoreva Mv, A S Nikonova, Finogenova Na, E A Mamedova, Polovtseva Tv, L Ia Fetisova, L A Gracheva, Goldyreva Ng
Abstract
L V Koval'chuk, Khoreva Mv, A S Nikonova, Finogenova Na, E A Mamedova, Polovtseva Tv, L Ia Fetisova, L A Gracheva, Goldyreva Ng
Abstract
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--TNF alpha and IFN alpha. Ligands for TLR1/2, TLR 2/6, TLR4, TLR5, and TLR9 were used to stimulate TNF alpha 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 IFN alpha. Levels of TNF alpha and IFN alpha 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 TNF alpha 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 IFN alpha 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.
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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--TNF alpha and IFN alpha. Ligands for TLR1/2, TLR 2/6, TLR4, TLR5, and TLR9 were used to stimulate TNF alpha 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 IFN alpha. Levels of TNF alpha and IFN alpha 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 TNF alpha 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 IFN alpha 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.
Key concepts: TLR2, TLR9, Neutropenia, Peripheral blood mononuclear cell, Immunology, TLR5, Medicine, TLR4