Interruption of Lymph Flow Worsens the Skin Inflammation Caused by Saprophytic Staphylococcus epidermidis.

Lymphedema is often complicated by chronic inflammation, leading to fibrosis, fat deposition, and inhibition of lymphangiogenesis. This study aimed to verify whether lymphedema itself or together with commensal bacterial flora infection contributes to the severity of local inflammation. Edema was induced by interruption of the lymph flow in the rat's hind limb. Immune cell infiltrates were examined by flow cytometry and immunohistochemistry. Nine-day edema alone did not affect immune cell content in the skin but resulted in a decrease in CD4+ T helper lymphocytes and monocytes in the draining popliteal lymph nodes. In turn, local saprophytic Staphylococcus epidermidis infection of the edematous limb resulted in dense infiltrates of CD68+ macrophages and monocytes, MHC class II antigen-presenting cells, CD90+ stem cells, thymocytes, and immature B cells in the skin, accompanied by a simultaneous reduction in density of CD4+ T helper lymphocytes and monocytes, OX62+ dendritic cells, CD68+ macrophages and monocytes, HiS48+ granulocytes, CD90+ stem cells, thymocytes, and immature B cells in the draining popliteal lymph nodes. These results indicate that the combination of edema and saprophytic bacteria infection induces severe inflammation in the peripheral tissues and results in a delay of antibacterial protection processes in neighboring lymphatic organs.

Towards Understanding the Lymph Node Response to Skin Infection with Saprophytic Staphylococcus epidermidis.

In individuals with lymphedema, diabetic foot, or other diseases, infections with saprophytes are common. The response of major cell subpopulations in the draining lymph nodes to skin infection with Staphylococcus epidermidis was assessed using the rat model. After massive subepidermal infection, a cytometric evaluation showed an increase in cytotoxic and helper T lymphocytes and major subpopulations of the innate immune response. Three weeks later, signs of inflammation reduction with an increase in the content of memory T helper lymphocytes and effector memory T cytotoxic lymphocytes were observed. After skin re-infection, a rapid response of cytotoxic, helper, and memory T lymphocytes, memory B lymphocytes and plasmablasts, and macrophages was detected. In addition, a reduction in the number of naïve B lymphocytes, activated MHC class II+ cells, and some cells of the innate immune system was observed. T regulatory lymphocyte response after the initial and secondary S. epidermidis skin infection was not detected. The morphometric evaluation showed significant changes in the main cell subpopulations in each functional zone of the node and then confirmed the efficient elimination of the administered antigen, as evidenced by the observations on day 28. Notably, after re-infection, the cellular response did not exceed the level after the initial infection and was reduced in many cell subpopulations. Understanding how the lymph nodes eliminate S. epidermidis can provide valuable insights into creating immunological therapies against infections with saprophytes.

Aging-Related Cellular, Structural and Functional Changes in the Lymph Nodes: A Significant Component of Immunosenescence? An Overview.

Aging affects all tissues and organs. Aging of the immune system results in the severe disruption of its functions, leading to an increased susceptibility to infections, an increase in autoimmune disorders and cancer incidence, and a decreased response to vaccines. Lymph nodes are precisely organized structures of the peripheral lymphoid organs and are the key sites coordinating innate and long-term adaptive immune responses to external antigens and vaccines. They are also involved in immune tolerance. The aging of lymph nodes results in decreased cell transport to and within the nodes, a disturbance in the structure and organization of nodal zones, incorrect location of individual immune cell types and impaired intercellular interactions, as well as changes in the production of adequate amounts of chemokines and cytokines necessary for immune cell proliferation, survival and function, impaired naïve T- and B-cell homeostasis, and a diminished long-term humoral response. Understanding the causes of these stromal and lymphoid microenvironment changes in the lymph nodes that cause the aging-related dysfunction of the immune system can help to improve long-term immune responses and the effectiveness of vaccines in the elderly.

Alterations in the Genomic Distribution of 5hmC in In Vivo Aged Human Skin Fibroblasts.

5-Hydroxymethylcytosine (5hmC) is a functionally active epigenetic modification. We analyzed whether changes in DNA 5-hydroxymethylation are an element of age-related epigenetic drift. We tested primary fibroblast cultures originating from individuals aged 22-35 years and 74-94 years. Global quantities of methylation-related DNA modifications were estimated by the dot blot and colorimetric methods. Regions of the genome differentially hydroxymethylated with age (DHMRs) were identified by hMeDIP-seq and the MEDIPS and DiffBind algorithms. Global levels of DNA modifications were not associated with age. We identified numerous DHMRs that were enriched within introns and intergenic regions and most commonly associated with the H3K4me1 histone mark, promoter-flanking regions, and CCCTC-binding factor (CTCF) binding sites. However, only seven DHMRs were identified by both algorithms and all of their settings. Among them, hypo-hydroxymethylated DHMR in the intron of Rab Escort Protein 1 (CHM) coexisted with increased expression in old cells, while increased 5-hydroxymethylation in the bodies of Arginine and Serine Rich Protein 1 (RSRP1) and Mitochondrial Poly(A) Polymerase (MTPAP) did not change their expression. These age-related differences were not associated with changes in the expression of any of the ten-eleven translocation (TET) enzymes or their activity. In conclusion, the distribution of 5hmC in DNA of in vivo aged human fibroblasts underwent age-associated modifications. The identified DHMRs are, likely, marker changes.

Targeting Abdominal Obesity and Its Complications with Dietary Phytoestrogens.

In the assessment of the health risk of an obese individual, both the amount of adipose tissue and its distribution and metabolic activity are essential. In adults, the distribution of adipose tissue differs in a gender-dependent manner and is regulated by sex steroids, especially estrogens. Estrogens affect adipocyte differentiation but are also involved in the regulation of the lipid metabolism, insulin resistance, and inflammatory activity of the adipose tissue. Their deficiency results in unfavorable changes in body composition and increases the risk of metabolic complications, which can be partially reversed by hormone replacement therapy. Therefore, the idea of the supplementation of estrogen-like compounds to counteract obesity and related complications is compelling. Phytoestrogens are natural plant-derived dietary compounds that resemble human estrogens in their chemical structure and biological activity. Supplementation with phytoestrogens may confer a range of beneficial effects. However, results of studies on the influence of phytoestrogens on body composition and prevalence of obesity are inconsistent. In this review, we present data from in vitro, animal, and human studies regarding the role of phytoestrogens in adipose tissue development and function in the context of their potential application in the prevention of visceral obesity and related complications.

Glucocorticoid receptor (NR3C1) gene polymorphisms are associated with age and blood parameters in Polish Caucasian nonagenarians and centenarians.

INTRODUCTION: Polymorphism of the glucocorticoid receptor gene (NR3C1) may modify protein abundance or function and therefore disturb human homeostasis. METHODS: Variant frequencies of the three NR3C1 polymorphisms, rs2963154, rs10515522 and rs2918418, selected in silico as associated with longevity, was analyzed in 552 DNA samples from 95 to 106-year-old individuals and in 284 samples of cord blood DNA from newborns. RESULTS: Frequencies of the TT genotypes of rs2963154 and rs10515522, and of the rs291841 CC genotype, were higher in the long-lived study subjects (p = 0.002, p = 0.016 and p = 0.028, respectively). In the long-lived cohort, the rs2963154 CC genotype was associated with higher concentrations of total (p = 0.007) and high-density cholesterol (p = 0.039). The rs10515522 CC genotype was associated with a higher concentration of total cholesterol (p = 0.049). The rs2918418 GG genotype was associated with higher concentrations of total (p = 0.03) and low-density cholesterol (p = 0.03). None of the polymorphisms was associated with fasting glucose, C-reactive protein levels and white blood count, prevalence of diabetes, stroke, myocardial infarction, or cognitive function. However, carriers of the rs10515522 minor allele had significantly better survival rates than carriers of other genotypes. CONCLUSION: NR3C1 polymorphisms modify cholesterol levels, and may affect the survival rates of individuals in their tenth and eleventh decades of life.