Staphylococcus aureus drives expansion of low-density neutrophils in diabetic mice

Diabetic individuals are at considerable risk for invasive infection by Staphylococcus aureus, however, the mechanisms underlying this enhanced susceptibility to infection are unclear. We observed increased mortality following i.v. S. aureus infection in diabetic mice compared with nondiabetic controls, correlating with increased numbers of low-density neutrophils (LDNs) and neutrophil extracellular traps (NETs). LDNs have been implicated in the inflammatory pathology of diseases such as lupus, given their release of large amounts of NETs. Our goal was to describe what drives LDN increases during S. aureus infection in the diabetic host and mechanisms that promote increased NET production by LDNs. LDN development is dependent on TGF-β, which we found to be more activated in the diabetic host. Neutralization of TGF-β, or the TGF-β–activating integrin αvβ8, reduced LDN numbers and improved survival during S. aureus infection. Targeting S. aureus directly with MEDI4893*, an α toxin–neutralizing monoclonal antibody, blocked TGF-β activation, reduced LDNs and NETs, and significantly improved survival. A comparison of gene and protein expression in high-density neutrophils and LDNs identified increased GPCRs and elevated phosphatase and tensin homolog (PTEN) in the LDN subset. Inhibition of PTEN improved the survival of infected diabetic mice. Our data identify a population of neutrophils in infected diabetic mice that correlated wit...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

Related Links:

CONCLUSION: Arterial hypertension and elevated diastolic blood pressure are associated with a risk for AS requiring surgery in subjects below 60 years of age. Strict blood pressure control in this group is strongly advocated to avoid other cardiovascular diseases correlated to hypertension. If hypertension and elevated diastolic blood pressure are risk factors for developing AS requiring surgery need further investigations. Notably, elevated fasting glucose levels were related to AS requiring surgery in older adults without concomitant CAD. PMID: 31109205 [PubMed - in process]
Source: Scandinavian Cardiovascular Journal - Category: Cardiology Tags: Scand Cardiovasc J Source Type: research
Conclusions: Glucose fluctuation aggravates mesangial cell apoptosis, which may be partly induced by activating oxidative stress and inhibiting the AKT signaling pathway. PMID: 31110541 [PubMed]
Source: Archives of Medical Science - Category: General Medicine Tags: Arch Med Sci Source Type: research
Authors: Grzelak T, Wedrychowicz A, Grupinska J, Pelczynska M, Sperling M, Mikulska AA, Naughton V, Czyzewska K Abstract Introduction: The aim of our study was to determine the relationship between neuropeptide B (NPB), neuropeptide W (NPW), nutritional and antioxidant status and selected fat- and bone-derived factors in type 1 diabetes mellitus (T1DM) treated using pens (T1DM pen group) or insulin pumps (T1DM pump group) in order to investigate the potential role of NPB and NPW in the clinical outcomes of T1DM. Material and methods: Fifty-eight patients with T1DM and twenty-five healthy controls (CONTR) partic...
Source: Archives of Medical Science - Category: General Medicine Tags: Arch Med Sci Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Gulcin Tezcan1, Ekaterina V. Martynova1, Zarema E. Gilazieva1, Alan McIntyre2, Albert A. Rizvanov1 and Svetlana F. Khaiboullina1,3* 1Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia 2Centre for Cancer Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, United Kingdom 3Department of Microbiology and Immunology, University of Nevada, Reno, Reno, NV, United States Inflammation has a crucial role in protection against various pathogens. The inflammasome is an intracellular multiprotein signaling complex that is linked to pathogen sensing and...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions In conclusion, articles in this Research Topic made a very significant contribution to our understanding of the role played by environmental factors, dysbiotic conditions, and infections in triggering diseases. Since this is a rapidly expanding area of research, many other factors contributing to the onset of these diseases are not covered here. We are confident, however, that further studies will expand the list as well as bring a better understanding of mechanisms involved in the onset of autoimmune and autoinflammatory diseases. Author Contributions All authors listed have made a substantial, direct and i...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
​BY AARON SNYDER, MDInfectious processes, such as streptococcal infections, can partially masquerade as alternative diagnosis. Streptococcal infections are a frequent source of infection treated by emergency physicians, and it is crucial that the appropriate tests, antibiotics, and hospitalization are used to recognize rash patterns and to identify causes and the differential of causation.A 60-year-old woman presented from her primary medical doctor's office with fever, fatigue, tachycardia, and facial discomfort for two days that developed into a malar rash. The patient reported one day of fever, several days of sore th...
Source: The Case Files - Category: Emergency Medicine Tags: Blog Posts Source Type: research
Since their discovery in patients with autosomal dominant (AD) chronic mucocutaneous candidiasis (CMC) in 2011, heterozygous STAT1 gain-of-function (GOF) mutations have increasingly been identified worldwide. The clinical spectrum associated with them needed to be delineated. We enrolled 274 patients from 167 kindreds originating from 40 countries from 5 continents. Demographic data, clinical features, immunological parameters, treatment, and outcome were recorded. The median age of the 274 patients was 22 years (range, 1-71 years); 98% of them had CMC, with a median age at onset of 1 year (range, 0-24 years). Patients oft...
Source: Blood - Category: Hematology Authors: Tags: Pediatric Hematology, Immunobiology, Free Research Articles, Clinical Trials and Observations Source Type: research
Conclusion Although hepatic abnormalities caused by daptomycin are rare, a handful of cases with daptomycin-induced liver injury have been reported in the literature. Of note, in most cases, patients on daptomycin therapy developed liver damage with elevations in CK levels. Our case report suggests possible severe liver injury associated with high-dose and long-term daptomycin treatment in the absence of rhabdomyolysis. Future research is warranted to further investigate the relationship between daptomycin use and liver injury, yet it is reasonable to monitor liver function tests at baseline and weekly thereafter along wit...
Source: Journal of Pharmacy Practice - Category: Drugs & Pharmacology Authors: Tags: Adverse Drug Events Source Type: research
Olecranon bursitis, also called baker’s or Popeye elbow, can be a painless or an irritating condition involving the bursa located near the proximal end of the ulna in the elbow over the olecranon. Normal bursae sacs generally are filled with a small amount of fluid, which helps the joint remain mobile. The sac can swell under the soft tissue from overuse or when the area sustains an injury from a bump or fall.   Normal bursae are usually small, but they can grow to be quite large, swollen, and occasionally even infected when they become irritated or inflamed. The swelling is obvious because the space in this a...
Source: The Procedural Pause - Category: Emergency Medicine Tags: Blog Posts Source Type: blogs
More News: Biomedical Science | Diabetes | Endocrinology | Genetics | Lupus | Pathology | Staphylococcus Aureus