Interactions between immunosuppressor neutrophiles, innate and adaptive immunity indexes in the patients with subclinical atherosclerosis

Abstract

The last fifteen years have been marked by rapid progress in the study of neutrophils. The discovery of transcriptional plasticity of neutrophils, their phenotypic and functional heterogeneity contributed to launching active interdisciplinary studies on the role of neutrophils in various chronic inflammatory diseases. Increased systemic circulation of immunosuppressive neutrophils can be observed not only in sepsis, but also in chronic systemic inflammation, which, along with disorders of lipid metabolism, is the major mechanism of atherosclerosis development and progression. Monocytes, dendritic cells, Tlymphocytes and neutrophils are key participants and modulators of inflammation in atherosclerosis. Potential significance of immunosuppressive neutrophils in atherogenesis and regulation of inflammatory response in atherosclerosis has not been currently established. However, taking into account their possible effects upon T lymphocytes and innate immunity cells, the study of immunosuppressive neutrophils seems promising in the context of atherosclerosis and atherosclerotic cardiovascular diseases. The purpose of this study was to evaluate relationship between the numbers of circulating immunosuppressive neutrophils and subpopulations of T cells and monocytes in the patients with subclinical atherosclerosis. The study enrolled patients aged 40-64 years with subclinical atherosclerosis of peripheral arteries. Subpopulations of neutrophils, lymphocytes and monocytes were phenotyped by flow cytometry using “Navios 6/2” (Beckman Coulter). 133 patients, 65 (48.8%) males and 68 (51.2%) females were included into the study. Correlation analysis showed that increased number of circulating CD16hiCD11bloCD62Lbr neutrophils was associated with increased number of regulatory T lymphocytes. The patients with subclinical atherosclerosis and absolute numbers of circulating immunosuppressive neutrophils within the first quartile (<136 cells/μL) had a statistically significantly lower number of regulatory T lymphocytes compared with patients in the 2-4 quartiles. An increase in immunosuppressive neutrophils was associated with decreased number of classical monocytes expressing TLR4 (r = -0.335; p = 0.004), and a decrease in TLR2 surface expression intensity (r = -0.268; p = 0.023) on the non-classical monocytes. In patients with subclinical atherosclerosis of 40-64 years old, an increase in immunosuppressive CD16hiCD11bloCD62Lbr neutrophils was associated with increase in regulatory T lymphocytes and nonclassical monocytes, as well as decrease in classic monocytes expressing TLR4, and lower intensity of TLR2 expression on the non-classical monocytes.

Keywords

• neutrophils
• immunosuppression
• t cells
• monocytes
• atherosclerosis