TLR-mediated activation of peripheral blood monocyte phagocytosis in patients with multiple sclerosis

Abstract

The aim of the study: to reveal peculiarities of the phagocytic activity of TLR4, TLR7/8-activated monocytes of peripheral blood, depending on the type of multiple sclerosis and clinical effectiveness of the treatment. Material and methods. E. coli or ssRNA40/LyoVec lipopolysaccharide as TLR4 and TLR7/8 agonists were added to the monocyte-enriched cell suspension, respectively, and incubated for 24 hours at t 37 °C under an atmosphere of 5 % CO2. In parallel series, ram erythrocytes (RE) sensitized with hemolytic serum and inactivated C. albicans cells were used as phagocytosis objects; the incubation time was 30 minutes. The phagocytic index was calculated as the percentage of phagocytic monocytes and the phagocytic number as the ratio of the total number of absorbed REs or C. albicans cells to the number of monocytes that entered into phagocytosis. The study presents the results of examination of 58 patients with recurring remitting (RRMS) and 36 patients with progressive (PMS) multiple sclerosis. Results. The differences in the activation mechanisms of peripheral blood monocytes in patients with PC, which consist in different phagocytic activity in response to stimulation of TLR4 and TLR 7/8 depending on the disease conditions, were presented. Phagocytic activity lesions of monocytes were observed both in patients with RRMS and PMS, associated mainly with FcR-mediated mechanisms of phagocytosis. IFN-β therapy in patients with RRMS led to the correction of such disorders in patients with high treatment efficacy (responders), and TLR7/8-mediated activation of monocytes was accompanied by an increase in the number of phagocytic cells. In patients with low efficacy of IFN-β therapy (nonresponders), the nature of changes in the phagocytic activity of stimulated monocytes indicated a decrease in the functional reserve with regard to FcR-mediated phagocytosis. Conclusions. The obtained results indicate differences in phagocytic activity indices during stimulation of TLR4 and TLR7/8 and may indicate the presence of functional and phenotypic alterations of peripheral blood monocytes depending on the effectiveness of MS treatment.

Keywords

• multiple sclerosis
• ifn-β
• phagocytic activity of monocytes
• toll-like receptors