Notes

Unique habits of illness activity as time passes throughout sufferers with energetic SLE uncovered using hidden school velocity types.
Immunosenescence is marked by a systemic process named inflammaging along with a series of defects in the immunological activity that results in poor responses to infectious agents and to vaccination. Inflammaging, a state of low-grade chronic inflammation, usually leads to chronic inflammatory diseases and frailty in the elderly. However, some elderly escape from frailty and reach advanced age free of the consequences of inflammaging. find more This process has been called immunological remodeling, and it is the hallmark of healthy aging as described in the studies of centenarians in Italy. The biological markers of healthy aging are still a matter of debate, and the studies on the topic have focused on inflammatory versus remodeling processes and molecules. The sub-clinical inflammatory status associated with aging might be a deleterious event for populations living in countries where chronic infectious diseases are not prevalent. Nevertheless, in other parts of the world where they are, two possibilities may occur. Inflammatory responses may have a protective effect against these infectious agents. At the same time, the long-term consequences of protective immune responses during chronic infections may result in accelerated immunosenescence in these individuals. Therefore, the biological markers of healthy aging can vary according to environmental, cultural, and geographical settings that reflect worldwide, and in a non-biased, non-westernized perspective, the changes that we experience regarding our contacts with microorganisms and the outcomes of such contacts.Chronic liver disease when accompanied by underlying fibrosis, is characterized by an accumulation of extracellular matrix (ECM) proteins and chronic inflammation. Although traditionally considered as a passive and largely architectural structure, the ECM is now being recognized as a source of potent damage-associated molecular pattern (DAMP)s with immune-active peptides and domains. In parallel, the ECM anchors a range of cytokines, chemokines and growth factors, all of which are capable of modulating immune responses. A growing body of evidence shows that ECM proteins themselves are capable of modulating immunity either directly via ligation with immune cell receptors including integrins and TLRs, or indirectly through release of immunoactive molecules such as cytokines which are stored within the ECM structure. Notably, ECM deposition and remodeling during injury and fibrosis can result in release or formation of ECM-DAMPs within the tissue, which can promote local inflammatory immune response and chemotactic immune cell recruitment and inflammation. It is well described that the ECM and immune response are interlinked and mutually participate in driving fibrosis, although their precise interactions in the context of chronic liver disease are poorly understood. This review aims to describe the known pro-/anti-inflammatory and fibrogenic properties of ECM proteins and DAMPs, with particular reference to the immunomodulatory properties of the ECM in the context of chronic liver disease. Finally, we discuss the importance of developing novel biotechnological platforms based on decellularized ECM-scaffolds, which provide opportunities to directly explore liver ECM-immune cell interactions in greater detail.Polymorphonuclear neutrophils (PMN) are critical for first line innate immune defence against Staphylococcus aureus. Mature circulating PMN maintain a short half-life ending in constitutive apoptotic cell death. This makes them unlikely candidates as a bacterial intracellular niche. However, there is significant evidence to suggest that S. aureus can survive intracellularly within PMN and this contributes to persistence and dissemination during infection. The precise mechanism by which S. aureus parasitizes these cells remains to be established. Herein we propose a novel mechanism by which S. aureus subverts both autophagy and apoptosis in PMN in order to maintain an intracellular survival niche during infection. Intracellular survival of S. aureus within primary human PMN was associated with an accumulation of the autophagic flux markers LC3-II and p62, while inhibition of the autophagy pathway led to a significant reduction in intracellular survival of bacteria. This intracellular survival of S. aureus was coupled with a delay in neutrophil apoptosis as well as increased expression of several anti-apoptotic factors. Importantly, blocking autophagy in infected PMN partially restored levels of apoptosis to that of uninfected PMN, suggesting a connection between the autophagic and apoptotic pathways during intracellular survival. These results provide a novel mechanism for S. aureus intracellular survival and suggest that S. aureus may be subverting crosstalk between the autophagic and apoptosis pathways in order to maintain an intracellular niche within human PMN.Invariant natural killer T (iNKT) cells are innate-like T lymphocytes. They quickly respond to antigenic stimulation by producing copious amounts of cytokines and chemokines. iNKT precursors differentiate into three subsets iNKT1, iNKT2, and iNKT17 with specific cytokine production signatures. link2 While key transcription factors drive subset differentiation, factors that regulate iNKT subset homeostasis remain incompletely defined. Transcriptomic analyses of thymic iNKT subsets indicate that Serpinb1a is one of the most specific transcripts for iNKT17 cells suggesting that iNKT cell maintenance and function may be regulated by Serpinb1a. Serpinb1a is a major survival factor in neutrophils and prevents cell death in a cell-autonomous manner. link3 It also controls inflammation in models of bacterial and viral infection as well as in LPS-driven inflammation. Here, we examined the iNKT subsets in neutropenic Serpinb1a-/- mice as well as in Serpinb1a-/- mice with normal neutrophil counts due to transgenic re-expression of SERPINB1 in neutrophils. In steady state, we found no significant effect of Serpinb1a-deficiency on the proliferation and numbers of iNKT subsets in thymus, lymph nodes, lung, liver and spleen. Following systemic activation with α-galactosylceramide, the prototypic glycolipid agonist of iNKT cells, we observed similar serum levels of IFN-γ and IL-4 between genotypes. Moreover, splenic dendritic cells showed normal upregulation of maturation markers following iNKT cell activation with α-galactosylceramide. Finally, lung instillation of α-galactosylceramide induced a similar recruitment of neutrophils and production of iNKT-derived cytokines IL-17, IFN-γ, and IL-4 in wild-type and Serpinb1a-/- mice. Taken together, our results indicate that Serpinb1a, while dominantly expressed in iNKT17 cells, is not essential for iNKT cell homeostasis, subset differentiation and cytokine release.[This corrects the article DOI 10.3389/fmicb.2018.00036.].Female sex workers (FSWs) represent a key population for the acquisition of sexually transmitted infections (STI) due to their social vulnerability and the risks associated with their occupation. This study was conducted to describe the sociodemographic characteristics and sexual behavior among FSWs in cities in northern Brazil, to determine the prevalence of human immunodeficiency virus 1 (HIV-1) and human T-cell lymphotropic virus (HTLV-1/2) infections and to identify the circulating subtypes of these agents in this key population. A cross-sectional study using the Time Location Sampling (TLS) method was conducted among 339 FSWs in cities in the state of Pará from 2005 to 2006. Serological and molecular tests were performed to identify infections and viral subtypes, and bivariate and multivariate analyses were conducted to identify risk factors. Most FSWs were young, single, less educated and had at least one child. The prevalence of antibodies against HIV-1 and HTLV-1 was 2.3 and 1.7%, respectively. HIV-1 subtypes B (87.5%) and F1 (12.5%) were identified among FSWs, as were Cosmopolitan subtype (1a) and Transcontinental subgroup (A). Unprotected sex and illicit drug use were associated with HIV-1 and HTLV-1 infections using bivariate and multivariate analyses, and age ≥27 years was associated only with HIV. The important information highlighted here clearly indicates that the lack of actions to control and prevent pathogens in FSWs and the lack of strategies for health promotion in key populations can further aggravate the epidemiological scenario of viral infections in remote areas with low human development indices. Neglecting these facts may be causing the spread of these two viruses and their respective subtypes in the general population of northern Brazil.Rifampin plays a crucial role in the treatment of staphylococcal implant-associated infection, as it is the only antibiotic capable of eradicating Staphylococcus aureus biofilms. However, the emergence of rifampin resistance strongly limits its use. Combinatorial therapy of antibiotics and bacteriophages may represent a strategy to overcome the resistance. Here, we evaluated the activity of staphylococcal bacteriophage Sb-1 in combination with different antibiotics against the biofilms of 10 rifampin-resistant S. aureus clinical strains, including MRSA and MSSA. S. aureus biofilms formed on porous glass beads were exposed to antibiotics alone or combined with Sb-1 simultaneously or staggered (first Sb-1 for 24 h followed by antibiotic). Recovered bacteria were detected by measuring growth-related heat production at 37°C (isothermal microcalorimetry) and the biofilm eradication was assessed by sonication of beads and plating of the resulting sonication fluid. Minimum biofilm eradication concentration (MBEC) was defined as the lowest concentration of antibiotic required to kill all adherent bacteria, resulting in absence of growth after plating the sonication fluid. Tested antibiotics presented high MBEC values when administered alone (64 to > 1,024 μg/ml). The simultaneous or staggered combination of Sb-1 with daptomycin showed the highest activity against all MRSA biofilms, whereas the exposure to Sb-1 with vancomycin showed no improved anti-biofilm activity. Staggered administration of Sb-1 and flucloxacillin, cefazolin, or fosfomycin improved the antibiofilm activity in four out of six MSSA, whereas simultaneous exposure exhibited similar or lesser synergy. In conclusion, the combinatorial effect of Sb-1 and antibiotics enabled to eradicate rifampin-resistant S. aureus biofilms in vitro.Candida albicans is an important human pathogen and a major concern in intensive care units around the world. C. albicans infections are associated with a high mortality despite the use of antifungal treatments. One of the causes of therapeutic failures is the acquisition of antifungal resistance by mutations in the C. albicans genome. Fluconazole (FLC) is one of the most widely used antifungal and mechanisms of FLC resistance occurring by mutations have been extensively investigated. However, some clinical isolates are known to be able to survive at high FLC concentrations without acquiring resistance mutations, a phenotype known as tolerance. Mechanisms behind FLC tolerance are not well studied, mainly due to the lack of a proper way to identify and quantify tolerance in clinical isolates. We proposed here culture conditions to investigate FLC tolerance as well as an easy and efficient method to identity and quantify tolerance to FLC. The screening of C. albicans strain collections revealed that FLC tolerance is pH- and strain-dependent, suggesting the involvement of multiple mechanisms.
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