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Patients with multiple sclerosis (MS) suffer with age an early immunosenescence process, which influence the treatment response and increase the risk of infections. We explored whether lipid-specific oligoclonal IgM bands (LS-OCMB) associated with highly inflammatory MS modify the immunological profile induced by age in MS. This cross-sectional study included 263 MS patients who were classified according to the presence (M+, n=72) and absence (M-, n=191) of LS-OCMB. CSF cellular subsets and molecules implicated in immunosenescence were explored. In M- patients, aging induced remarkable decreases in absolute CSF counts of CD4+ and CD8+ T lymphocytes, including Th1 and Th17 cells, and of B cells, including those secreting TNF-alpha. It also increased serum anti-CMV IgG antibody titers (indicative of immunosenescence) and CSF CHI3L1 levels (related to astrocyte activation). In contrast, M+ patients showed an age-associated increase of TIM-3 (a biomarker of T cell exhaustion) and increased values of CHI3L1, independently of age. Finally, in both groups, age induced an increase in CSF levels of PD-L1 (an inductor of T cell tolerance) and activin A (part of the senescence-associated secretome and related to inflammaging). These changes were independent of the disease duration. Finally, this resulted in augmented disability. In summary, all MS patients experience with age a modest induction of T-cell tolerance and an activation of the innate immunity, resulting in increased disability. Additionally, M- patients show clear decreases in CSF lymphocyte numbers, which could increase the risk of infections. Thus, age and immunological status are important for tailoring effective therapies in MS.The peripheral nervous system consists of sensory circuits that respond to external and internal stimuli and effector circuits that adapt physiologic functions to environmental challenges. Identifying neurotransmitters and neuropeptides and the corresponding receptors on immune cells implies an essential role for the nervous system in regulating immune reactions. Vice versa, neurons express functional cytokine receptors to respond to inflammatory signals directly. Recent advances in single-cell and single-nuclei sequencing have provided an unprecedented depth in neuronal analysis and allowed to refine the classification of distinct neuronal subsets of the peripheral nervous system. Delineating the sensory and immunoregulatory capacity of different neuronal subsets could inform a better understanding of the response happening in tissues that coordinate physiologic functions, tissue homeostasis and immunity. Here, we summarize current subsets of peripheral neurons and discuss neuronal regulation of immune responses, focusing on neuro-immune interactions in the gastrointestinal tract. The nervous system as a central coordinator of immune reactions and tissue homeostasis may predispose for novel promising therapeutic approaches for a large variety of diseases including but not limited to chronic inflammation.Chronic inflammation plays an important role in the development of metabolic diseases. These include obesity, type 2 diabetes mellitus, and metabolic dysfunction-associated fatty liver disease. The proinflammatory environment maintained by the innate immunity, including macrophages and related cytokines, can be influenced by adaptive immunity. The function of T helper 17 (Th17) and regulatory T (Treg) cells in this process has attracted attention. The Th17/Treg balance is regulated by inflammatory cytokines and various metabolic factors, including those associated with cellular energy metabolism. The possible underlying mechanisms include metabolism-related signaling pathways and epigenetic regulation. Several studies conducted on human and animal models have shown marked differences in and the important roles of Th17/Treg in chronic inflammation associated with obesity and metabolic diseases. Moreover, Th17/Treg seems to be a bridge linking the gut microbiota to host metabolic disorders. In this review, we have provided an overview of the alterations in and the functions of the Th17/Treg balance in metabolic diseases and its role in regulating immune response-related glucose and lipid metabolism.Aspergillus fumigatus airway infections are associated with increased rates of hospitalizations and declining lung function in patients with chronic lung disease. While the pathogenesis of invasive A. fumigatus infections is well studied, little is known about the development and progression of airway infections. Previous studies have demonstrated a critical role for the IL-1 cytokines, IL-1α and IL-1β in enhancing pulmonary neutrophil recruitment during invasive aspergillosis. Here we use a mouse model of A. fumigatus airway infection to study the role of these IL-1 cytokines in immunocompetent mice. In the absence of IL-1 receptor signaling, mice exhibited reduced numbers of viable pulmonary neutrophils and increased levels of neutrophil apoptosis during fungal airway infection. Impaired neutrophil viability in these mice was associated with reduced pulmonary and systemic levels of G-CSF, and treatment with G-CSF restored both neutrophil viability and resistance to A. fumigatus airway infection. Taken together, these data demonstrate that IL-1 dependent G-CSF production plays a key role for host resistance to A. fumigatus airway infection through suppressing neutrophil apoptosis at the site of infection.

Rosacea, a chronic inflammatory skin disorder etiologically associated with immune cells and the antibacterial peptide cathelicidin LL-37, can be effectively treated by oral carvedilol administration.

To investigate the molecular mechanisms underlying carvedilol efficacy in rosacea treatment.

Skin samples of patients with rosacea were subjected to histopathological (hematoxylin and eosin) and immunohistochemical (CD68, Toll-like receptor 2 (TLR2), kallikrein 5, cathelicidin, TNF-α, and IL-1β) evaluation. An

murine rosacea-like inflammation model was established by LL-37 intradermal injection with or without carvedilol gavage-based pretreatment. Erythema proportion (Image J) and skin redness (L*a*b colorimetry) were quantified. Murine skin samples underwent pathological examination for inflammatory status and immunofluorescence staining. Murine skin and lipopolysaccharide-stimulated RAW 264.7 cells with or without carvedilol pretreatment were evaluated by quantitative reverse transcription-polymerase ge TLR2 expression as a novel anti-inflammatory mechanism.[This corrects the article DOI 10.3389/fmicb.2021.646748.].Wheat-originated microbes play an important role in shaping the quality of high-temperature Daqu which is commonly used as a starter for producing sauce-flavor Baijiu. However, the shifts of microbiota from raw material to fresh Daqu and then to mature Daqu remain unclear. Hence, in the present study, the inner and outer of fresh and mature Daqu were collected to explore the correlation between microbiota and metabolites as well as the source of the microbiota in Daqu. Results indicated that the activities of amylase and protease between the inner and outer of fresh Daqu varied significantly while both parts became similar after maturation. The predominant bacteria shifted from Saccharopolyspora (outer) and Staphylococcus (inner) to Kroppenstedtia (both outer and inner), while the predominant fungi shifted from Thermoascus (both outer and inner) to Byssochlamys (outer) and Fusarium (inner). A combining analysis of headspace solid-phase micro extraction-gas chromatography-mass spectrometry, headspace gas chromatography-ion mobility spectrometry, and nuclear magnetic resonance was employed to detect the metabolites. The network analysis was conducted to perform the relationships between microbes and metabolites. The results showed that the bacteria, especially Saccharopolyspora, Bacillus, and Acinetobacter, had a strong correlation with the productions of esters, amino acids and their derivatives, and sugars and their derivatives, while most fungi such as Thermoascus, were negatively correlated with the phenylalanine, trimethylamine n-oxide, and isovalerate. SourceTracker analysis indicated that wheat was the important source of the Daqu microbiota, especially, the microorganisms in the inner of Daqu might be the drivers of the microbial succession during maturation. This study provided a comprehensive exploration to understand the microbial sources and shifts in high-temperature Daqu during maturation.The increasing availability of modern research tools has enabled a revolution in studies of non-model organisms. Yet, one aspect that remains difficult or impossible to control in many model and most non-model organisms is the presence and composition of the host-associated microbiota or the microbiome. In this review, we explore the development of axenic (microbe-free) mosquito models and what these systems reveal about the role of the microbiome in mosquito biology. Additionally, the axenic host is a blank template on which a microbiome of known composition can be introduced, also known as a gnotobiotic organism. Finally, we identify a "most wanted" list of common mosquito microbiome members that show the greatest potential to influence host phenotypes. We propose that these are high-value targets to be employed in future gnotobiotic studies. The use of axenic and gnotobiotic organisms will transition the microbiome into another experimental variable that can be manipulated and controlled. Through these efforts, the mosquito will be a true model for examining host microbiome interactions.[This corrects the article DOI 10.3389/fmicb.2018.02329.].Lake littoral zones can also be regarded as another extremely hypersaline environment due to hypersaline properties of salt lakes. In this study, high-throughput sequencing technique was used to analyze bacteria and fungi from different rhizocompartments (rhizosphere and endosphere) of four dominant plants along the salinity gradient in the littoral zones of Ejinur Salt Lake. The study found that microbial α-diversity did not increase with the decrease of salinity, indicating that salinity was not the main factor on the effect of microbial diversity. JAK cancer Distance-based redundancy analysis and regression analysis were used to further reveal the relationship between microorganisms from different rhizocompartments and plant species and soil physicochemical properties. Bacteria and fungi in the rhizosphere and endosphere were the most significantly affected by SO4 2-, SOC, HCO3 -, and SOC, respectively. Correlation network analysis revealed the potential role of microorganisms in different root compartments on the regulation of salt stress through synergistic and antagonistic interactions. LEfSe analysis further indicated that dominant microbial taxa in different rhizocompartments had a positive response to plants, such as Marinobacter, Palleronia, Arthrobacter, and Penicillium. This study was of great significance and practical value for understanding salt environments around salt lakes to excavate the potential microbial resources.The accumulation of petroleum-based plastic waste has become a major issue for the environment. A sustainable and biodegradable solution can be found in Polyhydroxyalkanoates (PHAs), a microbially produced biopolymer. An analysis of the global phylogenetic and ecological distribution of potential PHA producing bacteria and archaea was carried out by mining a global genome repository for PHA synthase (PhaC), a key enzyme involved in PHA biosynthesis. Bacteria from the phylum Actinobacteria were found to contain the PhaC Class II genotype which produces medium-chain length PHAs, a physiology until now only found within a few Pseudomonas species. Further, several PhaC genotypes were discovered within Thaumarchaeota, an archaeal phylum with poly-extremophiles and the ability to efficiently use CO2 as a carbon source, a significant ecological group which have thus far been little studied for PHA production. Bacterial and archaeal PhaC genotypes were also observed in high salinity and alkalinity conditions, as well as high-temperature geothermal ecosystems.

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