Increased frequency of CD14+HLA-DR-/low cells in type 2 diabetes patients with poor glycemic control.

AIMS: Type 2 diabetes (T2DM) is associated with alterations of the immune response and T2DM patients have an increased risk for infections and certain sorts of cancers. Although CD14+HLA-DR-/low cells have emerged as important mediators of immunosuppression in several pathologies, including cancer and non-malignant diseases, the presence of these cells in T2DM is not fully characterized. METHODS: In this study, we evaluated the frequency of CD14+HLA-DR-/low cells in non-obese T2DM patients and their association with glycemic control. Peripheral blood mononuclear cells were isolated from healthy controls (HC, n = 24) and non-obese T2DM patients (n = 25), the population was evaluated by flow cytometry, and an analysis of correlation between cell frequencies and clinical variables was performed. RESULTS: CD14+HLA-DR-/low monocytes were expanded in patients with T2DM compared to HC regardless of weight. Among the subjects with T2DM, the frequency of CD14+HLA-DR-/low was higher in patients with poor glycemic control (HbA1c > 9%) compared to those with better glycemic control (HbA1c < 9%) and, positively correlated with the years since the diagnosis of T2DM, the age of the patients and the glycemic index. CONCLUSIONS: An increased frequency of CD14+HLA-DR-/low cells in the blood of T2DM patients was recorded. The influence of hyperglycemia seems to be independent of obesity, but related to glycemic control and age.

Type 2 diabetes mellitus metabolic control correlates with the phenotype of human monocytes and monocyte-derived macrophages.

AIMS: Monocytes and macrophages express cell-surface markers indicative of their inflammatory and activation status. In this study, we investigated whether these markers are affected or correlated in non-obese T2D subjects, or glycemic/metabolic control variables. METHODS: Clinical data was recorded, and peripheral blood drawn from T2D patients (n = 28) and control subjects (n = 27). Isolated monocytes were evaluated by flow cytometry for the expression of CD14, CD16, and the phenotypic markers for the different states of activation spectrum, such as pro-inflammatory (M1) (HLA-DR, CD86), anti-inflammatory/pro-resolving (M2) (CD163, CD206, MERTK, PD-L1) and metabolically-activated (MMe) (CD36, ABCA-1). From a subset of individuals, monocytes-derived macrophages (MDM) were obtained and evaluated for phenotypic markers. A correlation analysis was performed between the clinical variables and the marker expression. RESULTS: The frequency of CD14++CD16- monocytes was lower in T2D patients and it correlates negatively with poor control in glycemic and metabolic variables. T2D monocytes expressed lower levels of HLA-DR, CD86, PD-L1, and CD163, which correlated negatively with poor metabolic control. In MDM from T2D patients, HLA-DR, CD86 and CD163 expression was lower and it inversely correlated with deficient glycemic or metabolic control parameters. CONCLUSION: The glycemic/metabolic control associated with T2D influences monocyte and MDM phenotypes toward an immune-suppressive phenotype.

C-type lectins with a sweet spot for Mycobacterium tuberculosis.

The pattern of receptors sensing pathogens onto host cells is a key factor that can determine the outcome of the infection. This is particularly true when such receptors belong to the family of pattern recognition receptors involved in immunity. Mycobacterium tuberculosis, the etiologic agent of tuberculosis interacts with a wide range of pattern-recognition receptors present on phagocytes and belonging to the Toll-like, Nod-like, scavenger and C-type lectin receptor families. A complex scenario where those receptors can establish cross-talks in recognizing pathogens or microbial determinants including mycobacterial components in different spatial and temporal context starts to emerge as a key event in the outcome of the immune response, and thus, the control of the infection. In this review, we will focus our attention on the family of calcium-dependent carbohydrate receptors, the C-type lectin receptors, that is of growing importance in the context of microbial infections. Members of this family appear to be key innate immune receptors of mycobacteria, capable of cross-talk with other pattern recognition receptors to induce or modulate the inflammatory context upon mycobacterial infection.