Bacteriophages (phages) are biological entities that have attracted a great deal of attention in recent years. They have been reported as the most abundant biological entities on the planet and their ability to impact the composition of bacterial communities is of great interest. In this review, we aim to explore where phages exist in natural and artificial environments and how they impact communities. The natural environment in this review will focus on the human body, soils, and the marine environment. In these naturally occurring environments there is an abundance of phages suggesting a role in the maintenance of bacterial community homeostasis. The artificial environment focuses on wastewater treatment plants, industrial processes, followed by pharmaceutical formulations. As in natural environments, the existence of bacteria in manmade wastewater treatment plants and industrial processes inevitably attracts phages. The presence of phages in these environments can inhibit the bacteria required for efficient water treatment or food production. Alternatively, they can have a positive impact by eliminating recalcitrant organisms. Finally, we conclude by describing how phages can be manipulated or formulated into pharmaceutical products in the laboratory for use in natural or artificial environments.

Obesity is defined as the excessive accumulation of body fat and is associated with an increased risk of developing major health problems such as cardiovascular disease, diabetes and stroke. There are clear sexual dimorphisms in the epidemiology, pathophysiology and sequelae of obesity and its accompanying metabolic disorders, with females often better protected compared to males. This protection has predominantly been attributed to the female sex hormone estrogen and differences in fat distribution. More recently, the sexual dimorphisms of obesity have also been attributed to the differences in the composition and function of the gut microbiota, and the intestinal immune system. This review will comprehensively summarize the pre-clinical and clinical evidence for these sexual dimorphisms and discuss the interplay between sex hormones, intestinal inflammation and the gut microbiome in obesity. Major gaps and limitations of this rapidly growing area of research will also be highlighted in this review.

Conclusions: IL18 neutralisation affords protection against DOCA/salt induced hypertension and renal inflammation. Thus. IL18 may represent a potential therapeutic target to treat hypertension and CKD.

IntroductionDepletion of mature B cells affords protection against experimental hypertension. However, whether B cell-mediated hypertension is dependent on differentiation into antibody-secreting cells (ASCs) remains unclear. Using the proteasome inhibitor, bortezomib, the present study tested the effect of ASC reduction on angiotensin II-induced hypertension.MethodsMale C57BL6/J mice were infused with angiotensin II (0.7 mg/kg/day; s.c.) for 28 days via osmotic minipump to induce hypertension. Normotensive control mice received saline infusion. Bortezomib (750 μg/kg) or vehicle (0.1% DMSO) was administered (i.v.) 3 days prior to minipump implantation, and twice weekly thereafter. Systolic blood pressure was measured weekly using tail-cuff plethysmography. Spleen and bone marrow B1 (CD19+B220−), B2 (B220+CD19+) and ASCs (CD138hiSca-1+Blimp-1+) were enumerated by flow cytometry. Serum immunoglobulins were quantified using a bead-based immunoassay.ResultsBortezomib treatment reduced splenic ASCs by ∼68% and ∼64% compared to vehicle treatment in normotensive (2.00 ± 0.30 vs. 0.64 ± 0.15 × 105 cells; n = 10–11) and hypertensive mice (0.52 ± 0.11 vs. 0.14 ± 0.02 × 105 cells; n = 9–11), respectively. Bone marrow ASCs were also reduced by bortezomib in both normotensive (4.75 ± 1.53 vs. 1.71 ± 0.41 × 103 cells; n = 9–11) and hypertensive mice (4.12 ± 0.82 vs. 0.89 ± 0.18 × 103 cells; n = 9–11). Consistent with ASC reductions, bortezomib reduced serum IgM and IgG2a in all mice. Despite these reductions in ASCs and antibody levels, bortezomib did not affect angiotensin II-induced hypertension over 28 days (vehicle: 182 ± 4 mmHg vs. bortezomib: 177 ± 7 mmHg; n = 9–11).ConclusionReductions in ASCs and circulating IgG2a and IgM did not ameliorate experimental hypertension, suggesting other immunoglobulin isotypes or B cell effector functions may promote angiotensin II-induced hypertension.

Metabolic syndrome (MetS) is a complex multifactorial disease that increases cardiovascular risk. Vascular dysfunction associated with MetS is strongly influenced by perivascular adipose tissue (PVAT) which acts as a reservoir for immune cells. Sexual dimorphisms of PVAT pathophysiology are poorly understood due to a lack of clinically relevant animal models of MetS that show metabolic disturbances in males and females. Using a new diet-induced model of MetS pathophysiology in both sexes, we characterised the aortic leukocyte profile and determined PVAT influence on vascular function. Six-week-old male and female C57BL/6 mice were fed either a high-fat diet (43% kcal) with high sugar and salt (10% high fructose and 0.9% NaCl; HFSS) in drinking water, or normal control diet (NCD) for 10 weeks. Physiological parameters were measured fortnightly. At endpoint, aorta with PVAT intact was isolated for leukocyte enumeration (flow cytometry) or for in vitro vascular reactivity (± PVAT; wire myography). Weight gain (NCD M: 29.3±0.5 g vs. MetS M: 37.5±1.0 g; NCD F: 23.6±0.7 g vs. MetS F: 28.9±1.2 g), fasting blood glucose (NCD M: 9.5±0.4 mmol/L vs. MetS M: 11.3 mmol/L; NCD F: 8.9±0.3 mmol/L vs. 10.4±0.5 mmol/L), blood cholesterol (NCD M: 125.0±3.0 mg/dL vs. MetS M: 177.5±6.5 mg/dL; NCD F: 96.7±2.9 mg/dL vs. MetS F: 130.7±3.4 mg/dL) and systolic blood pressure (NCD M: 121.0±1.8 mmHg vs. MetS M: 132.0±2.1 mmHg; NCD F: 122.3±2.2 mmHg vs. MetS F: 133.6±2.7 mmHg) were increased in both sexes of HFSS-fed mice (P<0.05 n= 12; vs. NCD) confirming that the HFSS model is a clinically relevant diet-induced model of MetS. Despite comparable metabolic disturbances in both sexes, aortic inflammation was only observed in males (increased pro-inflammatory monocytes (Ly6C hi+ ; M: 3.3±0.5 x 10 3 cells/aorta vs F: 1.6±0.4 x 10 3 cells/aorta) and neutrophils (Ly6G + ; M: 0.9±-0.2 x 10 3 cells/aorta vs F: 0.3+/0.1 x 10 3 cells/aorta); P<0.05 vs. HFSS-fed female. MetS altered PVAT and vascular function in both sexes, but with contrasting effects. PVAT blunted endothelium-dependent relaxation in HFSS-fed males (P<0.05 vs. NCD male) and in NCD-fed females (P<0.05 vs. HFSS females). The data indicates that sexual dimorphisms in PVAT impacts MetS-induced aortic inflammation and endothelial dysfunction.