Identification of differentially expressed genes, pathways, and immune infiltration in diabetes.

This study aimed to perform exhaustive bioinformatic analysis by using GSE29221 micro-array maps obtained from healthy controls and Type 2 Diabetes (T2DM) patients. Raw data are downloaded from the Gene Expression Omnibus database and processed by the limma package in R software to identify Differentially Expressed Genes (DEGs). Gene ontology functional analysis and Kyoto Gene Encyclopedia and Genome Pathway analysis are performed to determine the biological functions and pathways of DEGs. A protein interaction network is constructed using the STRING database and Cytoscape software to identify key genes. Finally, immune infiltration analysis is performed using the Cibersort method. This study has implications for understanding the underlying molecular mechanism of T2DM and provides potential targets for further research.

Understanding how pre- and probiotics affect the gut microbiome and metabolic health.

The gut microbiome, a complex assembly of microorganisms, significantly impacts human health by influencing nutrient absorption, the immune system, and disease response. These microorganisms form a dynamic ecosystem that is critical to maintaining overall well-being. Prebiotics and probiotics are pivotal in regulating gut microbiota composition. Prebiotics nourish beneficial bacteria and promote their growth, whereas probiotics help maintain balance within the microbiome. This intricate balance extends to several aspects of health, including maintaining the integrity of the gut barrier, regulating immune responses, and producing metabolites crucial for metabolic health. Dysbiosis, or an imbalance in the gut microbiota, has been linked to metabolic disorders such as type 2 diabetes, obesity, and cardiovascular disease. Impaired gut barrier function, endotoxemia, and low-grade inflammation are associated with toll-like receptors influencing proinflammatory pathways. Short-chain fatty acids derived from microbial fermentation modulate anti-inflammatory and immune system pathways. Prebiotics positively influence gut microbiota, whereas probiotics, especially Lactobacillus and Bifidobacterium strains, may improve metabolic outcomes, such as glycemic control in diabetes. It is important to consider strain-specific effects and study variability when interpreting these findings, highlighting the need for further research to optimize their therapeutic potential. The aim of this report is therefore to review the role of the gut microbiota in metabolic health and disease and the effects of prebiotics and probiotics on the gut microbiome and their therapeutic role, integrating a broad understanding of physiological mechanisms with a clinical perspective.

High Glucose Concentrations Impair the Processing and Presentation of Mycobacterium tuberculosis Antigens In Vitro.

Type 2 diabetes is an established risk factor for tuberculosis, but the underlying mechanisms are largely unknown. We established an in vitro model to analyze the effect of high glucose concentrations in antigen processing and presentation in antigen-presenting cells. Human monocyte-derived macrophages (MDMs) were exposed to high (11 mM and 30 mM) and low (5.5 mM) glucose concentrations and infected with Mycobacterium tuberculosis (Mtb). Flow cytometry was used to analyze the effect of high glucose concentrations in histocompatibility complex (MHC) class II molecules (HLA-DR) and co-stimulatory molecules (CD80 and CD86), indispensable for an adequate antigenic presentation and CD4+ T cell activation. HLA-DR and CD86 were significantly decreased by high glucose concentrations compared with low glucose concentrations. Confocal microscopy was used to detect Rab 5 and Lamp-1, proteins involved in the kinetics of antigen processing as early markers, and Rab 7 and cathepsin D as late markers. We observed a delay in the dynamics of the acquisition of Rab 7 and cathepsin D in high glucose concentrations. Moreover, the kinetics of the formation M. tuberculosis peptide-MHC II complexes in MDMs was decreased under high glucose concentrations, reducing their capacity for T cell activation. These findings suggest that high glucose concentrations directly affect antigenic processing, and therefore antigenic presentation.

Gene signatures of autopsy lungs from obese patients with COVID-19.

BACKGROUND & AIMS: Obesity is associated with low grade systemic inflammation and insulin resistance. Although metabolic and immunological changes may contribute to the increased risk for COVID-19 mortality in obese, little is known about the impact of obesity in the lungs of patients with COVID-19. METHODS: We analyzed gene expression profiles of autopsy lungs of a cohort of 14 COVID-19 patients and 4 control individuals. Patients were divided into 3 groups according to their comorbidities: hypertension, type 2 diabetes (T2D) and obesity. We then identified the molecular alterations associated with these comorbidities in COVID-19 patients. RESULTS: Patients with only hypertension showed higher levels of inflammatory genes and B-cell related genes when compared to those with T2D and obesity. However, the levels of IFN-gamma, IL22, and CD274 (a ligand that binds to receptor PD1) were higher in COVID-19 patients with T2D and obesity. Several metabolic- and immune-associated genes such as G6PD, LCK and IL10 were significantly induced in the lungs of the obese group. CONCLUSION: Our findings suggest that SARS-CoV-2 infection in the lungs may exacerbate the immune response and chronic condition in obese COVID-19 patients.

Potential of Sulforaphane as a Natural Immune System Enhancer: A Review.

Brassicaceae are an outstanding source of bioactive compounds such as ascorbic acid, polyphenols, essential minerals, isothiocyanates and their precursors, glucosinolates (GSL). Recently, GSL gained great attention because of the health promoting properties of their hydrolysis products: isothiocyanates. Among them, sulforaphane (SFN) became the most attractive one owing to its remarkable health-promoting properties. SFN may prevent different types of cancer and has the ability to improve hypertensive states, to prevent type 2 diabetes-induced cardiomyopathy, and to protect against gastric ulcer. SFN may also help in schizophrenia treatment, and recently it was proposed that SFN has potential to help those who struggle with obesity. The mechanism underlying the health-promoting effect of SFN relates to its indirect action at cellular level by inducing antioxidant and Phase II detoxifying enzymes through the activation of transcription nuclear factor (erythroid-derived 2)-like (Nrf2). The effect of SFN on immune response is generating scientific interest, because of its bioavailability, which is much higher than other phytochemicals, and its capacity to induce Nrf2 target genes. Clinical trials suggest that sulforaphane produces favorable results in cases where pharmaceutical products fail. This article provides a revision about the relationship between sulforaphane and immune response in different diseases. Special attention is given to clinical trials related with immune system disorders.

Innate Immunity Alterations in Type 2 Diabetes Mellitus: Understanding Infection Susceptibility.

Diabetes is a chronic disease characterized by marked alterations in the metabolism of glucose and by high concentrations of glucose in the blood due to a decreased insulin production or resistance to the action of this hormone in peripheral tissues. The International Diabetes Federation estimates a global incidence of diabetes of about 10% in the adult population (20 - 79 years old), some 430 million cases reported worldwide in 2018. It is well documented that people with diabetes have a higher susceptibility to infectious diseases and therefore show higher morbidity and mortality compared to the non-diabetic population. Given that the innate immune response plays a fundamental role in protecting against invading pathogens through a myriad of humoral and cellular mechanisms, the present work makes a comprehensive review of the innate immune alterations in patients with type 2 diabetes mellitus (T2D) as well as a brief description of the molecular events leading or associated to such conditions. We show that in these patients a compromised innate immune response increases susceptibility to infections.

Recreational Dance Practice Modulates Lymphocyte Profile and Function in Diabetic Women.

This study aimed to investigate the impact of a 16-week dance-based aerobic exercise program on lymphocyte function in healthy and type 2 diabetes mellitus (T2DM) women. We enrolled 23 women: 11 with T2DM and 12 non-diabetic controls. Initially, we performed anthropometry and body composition measurements, afterwards, plasma levels of C-reactive protein, lipids, and glucose were determined. We used flow cytometry to measure the CD25 and CD28 expression in circulating lymphocytes, T-regulatory (Treg) cell percentage, lymphocyte proliferation, and cytokines released by cultured lymphocytes. The T2DM group had a lower proportion of CD28+ cells and a higher percentage of Treg lymphocytes and proliferative capacity at the baseline compared with the control group. After 16 weeks of the program, differences in lymphocytes between the T2DM and the control groups disappeared. The dance program promoted IL-10 increase in both groups. We found decreased IL-4, IL-2, and IL-6 secretion in lymphocytes from the control group and increased IL-17 secretion and IL-10/IL-17 ratio in the T2DM group after the program. The program promoted marked changes in lymphocytes in diabetic women, leading to a balance between the different profiles.

Preliminary findings on the possible role of B-lymphocyte stimulator (BLyS) on diabetes-related periodontitis.

The possible role of B-cell growth and differentiation-related cytokines on the pathogenesis of diabetes-related periodontitis has not been addressed so far. The aim of this study was to evaluate the effects of diabetes mellitus (DM) on the gene expression of proliferation-inducing ligand (APRIL) and B-lymphocyte stimulator (BLyS), two major cytokines associated to survival, differentiation and maturation of B cells in biopsies from gingival tissue with periodontitis. Gingival biopsies were obtained from subjects with periodontitis (n = 17), with periodontitis and DM (n = 19) as well as from periodontally and systemically healthy controls (n = 10). Gene expressions for APRIL, BLyS, RANKL, OPG, TRAP and DC-STAMP were evaluated using qPCR. The expressions APRIL, BLyS, RANKL, OPG, TRAP and DC-STAMP were all higher in both periodontitis groups when compared to the control group (p < 0.05). Furthermore, the expressions of BLyS, TRAP and RANKL were significantly higher in the subjects with periodontitis and DM when compared to those with periodontitis alone (p < 0.05). The mRNA levels of BLyS correlated positively with RANKL in the subjects with periodontitis and DM (p < 0.05). BLyS is overexpressed in periodontitis tissues of subjects with type 2 DM, suggesting a possible role of this cytokine on the pathogenesis DM-related periodontitis.

Evidence for a More Disrupted Immune-Endocrine Relation and Cortisol Immunologic Influences in the Context of Tuberculosis and Type 2 Diabetes Comorbidity.

Pulmonary tuberculosis (PTB), caused by Mycobacterium tuberculosis (Mtb), is a major health problem worldwide, further aggravated by the convergence of type 2 diabetes mellitus (DM) which constitutes an important risk factor for TB development. The worse scenario of patients with PTB and DM may be partly related to a more unbalanced defensive response. As such, newly diagnosed PTB patients with DM (TB+DM, n = 11) or not (TB, n = 21), as well as DM (n = 18) patients and pair matched controls (Co, n = 22), were investigated for the circulating immuno-endocrine-metabolic profile (ELISA), along with studies in peripheral blood mononuclear cells (PBMC) analyzing transcript expression (RT-qPCR) of mediators involved in glucocorticoid functionality. Given the hyperglycemic/hypercortisolemic scenario of TB+DM patients, PBMC were also exposed to stress-related cortisol concentrations (0.1 and 1 µM) and supraphysiologic glucose doses (10, 20, and 40 mM) and assessed for the specific response against Mtb stimulation (lymphoproliferation, -thymidine incorporation-, and cytokine production -bead-cytometry). All TB patients displayed increased plasma amounts of cortisol, growth hormone -hGH-, and proinflammatory mediators. In turn, TB+DM showed even higher levels of interferon gamma -IFN-γ- and hGH (vs. TB), or IL-6, C reactive protein, cortisol and hGH (vs. DM). Both DM groups had equally augmented values of IL-10. All TB patients showed decreased dehydroepiandrosterone- sulfate concentrations, even more in TB+DM cases. Leptin was also decreased in both TB cases, particularly in the TB group, revealing a lower body mass index, as well. Unlike PBMC from TB cases showing a decreased relationship between the glucocorticoids receptor (GR) isoforms (GRα/GRß; functional isoform/negative isoform), cells from TB+DM patients had no changes in this regard, along with an increased expression of 11-beta hydroxysteroid dehydrogenase type-1, the enzyme facilitating intracellular cortisone to cortisol conversion. TB+DM patients also showed an increased Mtb antigen-driven lymphoproliferation. Compared to TB, DM and HCo counterparts, PBMC from TB+DM patients had a biased Th1 response to Mtb stimulation (increased IL-2 and IFN-γ production), even when exposed to inhibitory cortisol doses. TB+DM patients show a more unbalanced immuno-endocrine relationship, respect the non-diabetic counterparts, with a relative deficiency of cortisol immunomodulatory influences, despite their more favorable microenvironment for cortisol-mediated immune effects.

M2 macrophage immunotherapy abolishes glucose intolerance by increasing IL-10 expression and AKT activation.

Aim: Glucose intolerance associates with M1/M2 macrophage unbalance. We thus wanted to examine the effect of M2 macrophage administration on mouse model of glucose intolerance. Materials & methods: C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks and then received thrice 20 mg/kg streptozotocin (HFD-GI). Bone marrow-derived stem cells were collected from donor mice and differentiated/activated into M2 macrophages for intraperitoneal administration into HFD-GI mice. Results: M2 macrophage treatment abolished glucose intolerance independently of obesity. M2 macrophage administration increased IL-10 in visceral adipose tissue and serum, but showed no effect on serum insulin. While nitric oxide synthase-2 and arginase-1 remained unaltered, M2 macrophage treatment restored AKT phosphorylation in visceral adipose tissue. Conclusion: M2 macrophage treatment abolishes glucose intolerance by increasing IL-10 and phosphorylated AKT.

Metformin promotes Mycobacterium tuberculosis killing and increases the production of human ß-defensins in lung epithelial cells and macrophages.

Diabetes has been associated with an increased risk of developing tuberculosis. The reasons related to the increased susceptibility to develop TB in type 2 diabetes mellitus (T2DM) individuals, has not been completely elucidated. However, this susceptibility has been attributed to several factors including failures and misfunctioning of the immune system. In the present study, we aimed to determine the role of anti-hyperglycemic drugs such as glyburide, insulin, and metformin to promote the killing of mycobacteria through the regulation of innate immune molecules such as host defense peptides (HDP) in lung epithelial cells and macrophages. Our results showed that metformin reduces bacillary loads in macrophages and lung epithelial cells which correlates with higher production of ß-defensin-2, -3 and -4. Since ß-defensins are crucial molecules for controlling Mycobacteriumtuberculosis growth, the present results suggest that the use of metformin would be the first choice in the treatment for T2DM2, in patients within tuberculosis-endemic areas.

Anti-Inflammatory Effect of Exercise Mediated by Toll-Like Receptor Regulation in Innate Immune Cells - A Review.

Over the last three decades, the combination of a sedentary lifestyle and excessive food intake has led to a significant increase in the prevalence of obesity. The latter favors a chronic low-grade inflammatory state and an over-activation of the innate immune system, which contribute to insulin resistance and type 2 diabetes. Physical exercise is a powerful preventive tool and treatment for several diseases as it induces metabolic and immune effects that provide health benefits. Exercise is known to reduce inflammation; however, the underlying mechanisms responsible are not fully elucidated. One proposed mechanism is a reduced expression and/or activation of pro-inflammatory toll-like receptors (TLRs) on innate immune cells after exercise, which could contribute to the protective effect of exercise against insulin resistance and the prevention of the development of metabolic diseases. The aim of the present study is therefore to review the current evidence about the anti-inflammatory effects of exercise and toll-like receptors regulation on immune cells in humans.Key PointsObesity leads to a low-grade chronic inflammatory state and an over-activation of the innate immune system that is directly involved in the develop metabolic syndrome.The anti-inflammatory effect of exercise has been previously suggested through the reduction of the expression and/or activation of pro-inflammatory toll-like receptors (TLRs) in innate immune cells, which represent one of the main inflammatory responses triggered by obesityThe underlying mechanisms in which toll-like receptors expression modulate the reduction of chronic inflammation are not fully elucidated.

Preliminary findings on the possible role of B-lymphocyte stimulator (BLyS) on diabetes-related periodontitis

Abstract The possible role of B-cell growth and differentiation-related cytokines on the pathogenesis of diabetes-related periodontitis has not been addressed so far. The aim of this study was to evaluate the effects of diabetes mellitus (DM) on the gene expression of proliferation-inducing ligand (APRIL) and B-lymphocyte stimulator (BLyS), two major cytokines associated to survival, differentiation and maturation of B cells in biopsies from gingival tissue with periodontitis. Gingival biopsies were obtained from subjects with periodontitis (n = 17), with periodontitis and DM (n = 19) as well as from periodontally and systemically healthy controls (n = 10). Gene expressions for APRIL, BLyS, RANKL, OPG, TRAP and DC-STAMP were evaluated using qPCR. The expressions APRIL, BLyS, RANKL, OPG, TRAP and DC-STAMP were all higher in both periodontitis groups when compared to the control group (p < 0.05). Furthermore, the expressions of BLyS, TRAP and RANKL were significantly higher in the subjects with periodontitis and DM when compared to those with periodontitis alone (p < 0.05). The mRNA levels of BLyS correlated positively with RANKL in the subjects with periodontitis and DM (p < 0.05). BLyS is overexpressed in periodontitis tissues of subjects with type 2 DM, suggesting a possible role of this cytokine on the pathogenesis DM-related periodontitis.

The Intracellular Growth of M. tuberculosis Is More Associated with High Glucose Levels Than with Impaired Responses of Monocytes from T2D Patients.

Diabetes mellitus, a metabolic disease characterized by hyperglycemia and poor glucose control, is a risk factor for Mycobacterium tuberculosis (M. tuberculosis) infection and the development of active tuberculosis. To evaluate whether M. tuberculosis infection susceptibility is associated with an intrinsic factor in monocytes from type 2 diabetes (T2D) patients or it is associated with hyperglycemia per se, we analyzed TLR-2 and TLR-4 expression by flow cytometry and the cytokines IL-1ß, IL-6, IL-8, IL-10, and TNF-α by cytometric bead array assays, either stimulated with TLR-2 and TLR-4 ligands or infected with M. tuberculosis in the whole blood from T2D patients (n = 43) and healthy subjects (n = 26) or in CD14+ monocytes from healthy subjects cultured in high glucose (HG) (30 mM). The intracellular growth of M. tuberculosis was evaluated by CFU counts at 0, 1, and 3 days in both monocytes from T2D patients and monocytes from healthy subjects cultured in HG. We did not find significant differences in TLR expression, cytokine production, or growth of M. tuberculosis in monocytes from T2D patients compared with those in monocytes from healthy subjects. Despite these results, in vitro assays of monocytes cultured with 30 mM glucose led to significantly increased TLR-2 and TLR-4 basal expression compared to those of monocytes cultured with 11 mM glucose (P < 0.05). Conversely, the production of IL-6 by TLR-2 ligand stimulation, of IL-1ß, IL-6, and IL-8 by TLR-4 ligand stimulation, and of IL-8 by M. tuberculosis infection significantly decreased in monocytes cultured in HG (P < 0.05). Additionally, the intracellular survival of M. tuberculosis increased in monocytes in HG after day 3 of culture (P < 0.05). In conclusion, HG decreased IL-8 production and the intracellular growth control of M. tuberculosis by monocytes, supporting the hypothesis that hyperglycemia plays an important role in the impaired immune responses to M. tuberculosis in patients with T2D.

Resistance Training Modulates the Humoral Inflammatory (but Not the DNA Methylation) Profile of Diabetic Older Adults Using Metformin.

BACKGROUND AND AIM: Inflammatory and methylation imbalances occur in patients with type 2 diabetes mellitus (T2DM). The aim of the present study was to analyze the effect of acute resistance exercise on the inflammatory profile and on DNA methylation of elderly patients with T2DM using metformin. METHODS: For this purpose, we enrolled 22 male and female older adults (68.2 ± 5.3 years), of whom 13 had controlled T2DM (D) under metformin use and 9 were nondiabetics (ND). All subjects underwent a neuromuscular circuit (8 exercises in 40 min, with each exercise performed in 3 sets of 40 s each and a 20-s interval between repetitions). RESULTS: The main results indicated a significant difference between groups for baseline interleukin (IL)-10, with a higher concentration in the D group compared to the ND group (p = 0.019). An increase in IL-6 concentration after intervention was observed in group D (p = 0.035). No effect was observed in total DNA methylation within or between groups. CONCLUSIONS: The resistance training protocol applied in this study modulates the IL-10 and IL-6 concentrations in elderly people with T2DM and under metformin use, possibly as a result of physiological adaptations, with no effect on nondiabetic elderly. No effects on absolute levels of DNA methylation were observed.

Phenotypic characterization of regulatory T cells populations in maternal blood, cord blood and placenta from diabetic mothers.

Purpose: Changes in regulatory T cells (Treg) in peripheral blood are associated with a number of pathologies, including diabetes. However, the immunological responses of pregnant diabetic women remain scarcely known, and the effects of Treg cells in these patients have yet to be investigated. The present study characterized the expression of regulatory T cells in the maternal blood, cord blood and placenta of diabetic pregnant women. Materials and methods: The women were divided according to glycemic status into a non-diabetic (ND; N = 20) or type 2 diabetic (T2DM; N = 20) group. Cell subsets were determined by flow cytometry. Results: Compared to ND, T2DM blood cells exhibited a higher expression of CD25+, Foxp3+, CD4+CD25+, CD4+Foxp3+ and CD25+Foxp3+; and cord blood cells showed a lower expression of CD25+, CD4+Foxp3+ and CD25+Foxp3+. In the placenta of T2DM, the villous layer of the proportion, CD3+ and CD25 was lower than that of CD4+Foxp3+ and CD25+Foxp3+, and the extravillous placenta layer contained the lowest levels of CD4+ and CD25+ and highest proportions of CD4+Foxp3+. In maternal blood from T2DM, the frequency of CD3+CD95+ and CD3CD4+ T cells expressing CD95+ was lower. In cord blood from T2DM, the rate of CD3+CD95+ was lower. The placenta villous layer of T2DM showed a lower count of CD3+CD95+ and of CD3CD4+ T cells expressing CD95+, whereas the number of cells expressing CD3+CD45RO+ decreased in both placental layers. Conclusion: The data obtained suggest that hyperglycemia changes the phenotypes of regulatory T cells and Fas expression in memory T cells.

Myeloid-Derived Suppressor Cells Show Different Frequencies in Diabetics and Subjects with Arterial Hypertension.

Type 2 diabetes mellitus (DM2) is strongly associated with other comorbidities such as obesity, atherosclerosis, and hypertension. Obesity is associated with sustained low-grade inflammatory response due to the production of proinflammatory cytokines. This inflammatory process promotes the differentiation of some myeloid cells, including myeloid-derived suppressor cells (MDSCs). In this study, two groups of individuals were included: DM2 patients and non-DM2 individuals with similar characteristics. Immunolabeling of CD15+ CD14- and CD33+ HLA-DR-/low was performed from whole peripheral blood, and samples were analyzed by flow cytometry, and frequencies of MDSCs and the relationship of these with clinical variables, cytokine profile (measured by cytometric bead array), and anthropometric variables were analyzed. The frequency of CD33+ HLA-DR-/low MDSCs (that produce IL-10 and TGF-ß, according to an intracellular detection) is higher in patients with DM2 (P < 0.05), and there is a positive correlation between the frequency of CD15+ CD14- and CD33+ HLA-DR-/low MDSC phenotypes. DM2 patients have an increased concentration of serum IL-5 (P < 0.05). Also, a negative correlation between the frequency of CD15+ CD14- MDSCs and LDL cholesterol was found. Our group of DM2 patients have an increased frequency of mononuclear MDSC CD33+ HLA-DR-/low that produce TGF-ß and IL-10. These cytokines have been associated with immune modulation and reduced T cell responses. DM2 and non-DM2 subjects show a similar cytokine profile, but the DM2 patients have an increased concentration of IL-5.

Obesity and Type 2 Diabetes mellitus induce lipopolysaccharide tolerance in rat neutrophils.

Obesity and diabetes implicate in various health complications and increased mortality caused by infection. Innate immune system is broadly affected by these diseases, leading the patients to an immunosuppressive state. A mechanism that leads innate immune cells to a less capacity of killing microorganism is the impaired TLR4 activation. TLR4 recognizes a component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS), and when activated increases the production of inflammatory substances. Neutrophils are components of the innate immune system and are the first responders to an invading agent. The correct activation of TLR4 in these cells is required for the initiation of the inflammatory process and elimination of the microorganisms. The aim of this study was to evaluate the influence of type 2 diabetes and obesity in the TLR4 pathway in rat neutrophils. Two experimental models were used: Goto-Kakizaki rats and high-fat-diet induced obese Wistar rats. To evaluate neutrophil response to LPS, intratracheal LPS instillation was used. Neutrophils from obese and diabetic animals exhibited tolerance to LPS, mainly by the impaired production of cytokines and chemokines and the low content of phospho-NFκB and phospho-IKBα. Neutrophils from both experimental models had increased cell death, impaired in vivo migration and myeloperoxidase activity.

Type-2 diabetes alters the basal phenotype of human macrophages and diminishes their capacity to respond, internalise, and control Mycobacterium tuberculosis.

BACKGROUND: Type 2 diabetes (T2D) is a risk factor for the development of tuberculosis (TB), although the associated mechanisms are not known. OBJECTIVES: To study the association between T2D and the basal phenotype of macrophages, and their immune response to Mycobacterium tuberculosis (Mtb) infection. METHODS: We evaluated the influence of T2D on the response of monocyte-derived macrophages (MDM) to Mtb in patients with T2D (n = 10) compared to healthy subjects (n = 9), before and after infection with Mtb clinical isolates bearing different degrees of virulence. The levels of cell surface markers for activation secreted cytokines and chemokines, bacterial association, and intracellular bacterial growth were evaluated. FINDINGS: The expression levels of HLA-DR, CD80, and CD86 were low while those of of PD-L1 were high in uninfected MDMs derived from patients with diabetes; as a result of Mtb infection, changes were only observed in the expression levels of PD-L1. The levels of cytokines (e.g., IL-6, IL-1ß, IL-10, and IL-12) and chemokines (e.g., MCP-1, MIG, and RANTES) are perturbed in MDMs derived from patients with diabetes, both before infection and in response to Mtb infection. In response to the more virulent Mtb strains, the levels of association and bacterial clearance were diminished in MDMs derived from patients with diabetes. CONCLUSIONS: T2D affects the basal activation state of the macrophages and its capacity to respond and control Mtb infection.

Host-Parasite Interactions in Individuals with Type 1 and 2 Diabetes Result in Higher Frequency of Ascaris lumbricoides and Giardia lamblia in Type 2 Diabetic Individuals.

Host-parasite interactions in diabetic patients might influence diabetes complications and intestinal parasitosis. The aim was to investigate the occurrence of enteroparasites in individuals with diabetes types 1 and 2. A descriptive study was designed to estimate frequencies of parasites and to compare them in individuals with diabetes types 1 and 2 from two Health Centers and one hospital in the Federal District of Brazil. Patients were allocated to the study by convenience. Three fecal samples of 156 diabetic individuals (120 type 1 and 36 type 2) were analyzed using two parasitological methods. Enteroparasites or commensals frequency in diabetics was 64%. Diabetics infected with up to six species of intestinal parasites or commensals were found. Frequencies of Ascaris lumbricoides and Giardia lamblia were higher in individuals with type 2 diabetes. The lower frequency of A. lumbricoides found in type 1 diabetes may be related to a strong Th2 response to parasites. Autoimmune response developed in type 1 diabetic individuals characterized by the production of Th1 cytokines could explain low frequency of G. lamblia. High frequency of parasites found in type 2 diabetes emphasizes the importance of periodic parasitological examinations in these individuals.