Microparticles derived from obese adipose tissue elicit a pro-inflammatory phenotype of CD16 + , CCR5 + and TLR8 + monocytes

Abstract

Macrophage infiltration into adipose tissue (AT) is a hallmark of the chronic inflammatory response in obesity and is supported by an intense monocyte migration towards AT. Although it has been detected an increased proportion of circulating CD16 monocyte subsets in obese subjects, the mechanisms underlying this effect and the contribution of these cells to the inflamed profile of obese AT are still poorly understood. We investigated whether factors secreted by human obese omental AT could polarize monocytes to CD16 enriched phenotype, and how these changes could modify their migratory capacity towards adipose tissue itself. We show that explants of human obese omental AT, obtained during bariatric surgery, released higher levels of MIP1-α, TNFα, leptin and also VEGF, together with increasing amounts of microparticles (MP), when compared to explants of lean subcutaneous AT. A higher content of circulating MP derived from preadipocytes and leukocytes was also detected in plasma of obese subjects. Conditioned media or MP released from obese omental AT increased CD16 and CCR5 expression on CD14CD16 monocytes and augmented their migratory capacity towards the conditioned media from obese omental AT, itself. This effect was inhibited when MIP1-α was neutralized. Additionally, we demonstrate that MP derived from obese omental AT carry and transfer TLR8 to monocytes, thus triggering an increase in CD16 expression in those cells. Our data shows a positive feedback loop between blood monocytes and obese omental AT, which releases chemotactic mediators and TLR8-enriched MP, thus inducing an up-regulation of CD16 monocytes, favoring leukocyte infiltration in the obese omental AT.

Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases

“…A similar phenomenon has been reported involving microparticles, HIV, and CXCR4 (Rozmyslowicz et al, 2003). CCR5 expression is also influenced by the release of EVs, specifically microparticles (Renovato-Martins et al, 2017). Therefore, EVs have the potential to attribute greater complexity to CCR5 roles in viral infections.…”

Hemostasis at Extremes of Body Weight

“…An increased proportion of circulating CD16 þ monocyte subsets is found in obese subjects, although the mechanisms underlying this effect and the contribution of these cells to the inflammatory state are unknown. Renovato-Martins et al 40 showed that explants of human obese omental adipose tissue, obtained during bariatric surgery, released higher levels of macrophage inflammatory protein 1-α (MIP1-α), tumor necrosis factor-α (TNF-α), leptin, and also vascular endothelial growth factor (VEGF), together with increasing amounts of MPs, when compared with explants of lean subcutaneous adipose tissue. Conditioned media or MPs released from obese omental adipocytes increased CD16 and CCR5 expression on CD14 þ CD16 À monocytes and augmented their migratory capacity toward the conditioned media from obese omental adipose tissue, itself, but was inhibited when MIP1-α was neutralized.…”

Comprehensive analysis of differential immunocyte infiltration and the potential ceRNA networks during epicardial adipose tissue development in congenital heart disease

“…Renovato-Martins et al demonstrate that monocyte infiltration into adipose tissue is a signature of organ early development, while macrophage infiltration is a hallmark of the inflammatory response in the adipose tissues of obesity patients [48]. Similarly, Wolf 's group found that the feedback loop between monocytes and macrophages not only provides immunological defense but also contributes to maintaining the function of EAT, which involves thermogenesis, metabolic balance, and local sympathetic nerve distribution [49].…”