These data suggest that proper function of Arg1 and arginine metabolism in myeloid cells remains essential to restrict amyloidosis.Acute myeloid leukemia (AML) is an aggressive myeloid malignancy with poor outcomes despite very intensive therapeutic approaches. For the majority of patients which are unfit and treated less intensively, the prognosis is even worse. There has been unspectacular progress in outcome improvement over the last decades and the development of new approaches is of tremendous interest. The tumor microenvironment is credited with an important role in supporting cancer growth, including leukemogenesis. Macrophages are part of the tumor microenvironment and their contribution in this setting is increasingly being deciphered, these cells being credited with a tumor supporting role. Data on macrophage role and polarization in leukemia is scarce. MicroRNAs (miRNAs) have a role in the post-transcriptional regulation of gene expression, by impending translation and promoting degradation of messenger RNAs. They are important modulators of cellular pathways, playing major roles in normal hematopoietic differentiation. miRNA , but data on correlations between miRNA expression and macrophage polarization is mostly coming from studies involving normal tissue.Postoperative ileus (POI) is triggered by an innate immune response in the muscularis externa (ME) and is accompanied by bacterial translocation. Bacteria can trigger an innate immune response via toll-like receptor (TLR) activation, but the latter's contribution to POI has been disproved for several TLRs, including TLR2 and TLR4. Herein we investigated the role of double-stranded RNA detection via TLR3 and TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling pathway in POI. POI was induced by small bowel intestinal manipulation in wt, TRIF-/-, TLR3-/-, type I interferon receptor-/- and interferon-β reporter mice, all on C57BL/6 background, and POI severity was quantified by gene expression analysis, gastrointestinal transit and leukocyte extravasation into the ME. TRIF/TLR3 deficiency reduced postoperative ME inflammation and prevented POI. With bone marrow transplantation, RNA-sequencing, flow cytometry and immunohistochemistry we revealed a distinct TLR3-expressing radio-resistant MHCIIhiCX3CR1- IBA-1+ resident macrophage population within the deep myenteric plexus. TLR3 deficiency in these cells, but not in MHCIIhiCX3CR1+ macrophages, reduced cytokine expression in POI. While this might not be an exclusive macrophage-privileged pathway, the TLR3/TRIF axis contributes to proinflammatory cytokine production in MHCIIhiCX3CR1- IBA-1+ macrophages during POI. Deficiency in TLR3/TRIF protects mice from POI. These data suggest that TLR3 antagonism may prevent POI in humans.Accumulated evidence has demonstrated that the macrophage phenotypic switch from M0 to M1 is crucial in the initiation of the inflammatory process of acute respiratory distress syndrome (ARDS). Better insight into the molecular control of M1 macrophages in ARDS may identify potential therapeutic targets. https://www.selleckchem.com/products/abt-199.html In the current study, 36 candidate genes associated with the severity of ARDS and simultaneously involved in M1-polarized macrophages were first screened through a weighted network algorithm on all gene expression profiles from the 26 ARDS patients and empirical Bayes analysis on the gene expression profiles of macrophages. STAT1, IFIH1, GBP1, IFIT3, and IRF1 were subsequently identified as hub genes according to connectivity degree analysis and multiple external validations. Among these candidate genes, IFIH1 had the strongest connection with ARDS through the RobustRankAggreg algorithm. It was selected as a crucial gene for further investigation. For in vitro validation, the RAW264.7 cell line and BMDMs were transfected with shIFIH1 lentivirus and plasmid expression vectors of IFIH1. Cellular experimental studies further confirmed that IFIH1 was a novel regulator for promoting M1 macrophage polarization. Moreover, gene set enrichment analysis (GSEA) and in vitro validations indicated that IFIH1 regulated M1 polarization by activating IRF3. In addition, previous studies demonstrated that activation of IFIH1-IRF3 was stimulated by viral RNAs or RNA mimics. Surprisingly, the current study found that LPS could also induce IFIH1-IRF3 activation via a MyD88-dependent mechanism. We also found that only IFIH1 expression without LPS or RNA mimic stimulation could not affect IRF3 activation and M1 macrophage polarization. These findings were validated on two types of macrophages, RAW264.7 cells and BMDMs, which expanded the knowledge on the inflammatory roles of IFIH1 and IRF3, suggesting IFIH1 as a potential target for ARDS treatment.Human infection by the SARS-CoV-2 is causing the current COVID-19 pandemic. With the growing numbers of cases and deaths, there is an urgent need to explore pathophysiological hypotheses in an attempt to better understand the factors determining the course of the disease. Here, we hypothesize that COVID-19 severity and its symptoms could be related to transmembrane and soluble Angiotensin-converting enzyme 2 (tACE2 and sACE2); Angiotensin II (ANG II); Angiotensin 1-7 (ANG 1-7) and angiotensin receptor 1 (AT1R) activation levels. Additionally, we hypothesize that an early peak in ANG II and ADAM-17 might represent a physiological attempt to reduce viral infection via tACE2. This viewpoint presents (1) a brief introduction regarding the renin-angiotensin-aldosterone system (RAAS), detailing its receptors, molecular synthesis, and degradation routes; (2) a description of the proposed early changes in the RAAS in response to SARS-CoV-2 infection, including biological scenarios for the best and worst prognoses; and (3) the physiological pathways and reasoning for changes in the RAAS following SARS-CoV-2 infection.T cells expressing high levels of inhibitory receptors such as PD-1 and LAG-3 are a hallmark of chronic infections and cancer. Checkpoint blockade therapies targeting these receptors have been largely validated as promising strategies to restore exhausted T cell functions and clearance of chronic infections and tumors. The inability to develop long-term natural immunity in malaria-infected patients has been proposed to be at least partially accounted for by sustained expression of high levels of inhibitory receptors on T and B lymphocytes. While blockade or lack of PD-1/PD-L1 and/or LAG-3 was reported to promote better clearance of Plasmodium parasites in various mouse models, how exactly blockade of these pathways contributes to enhanced protection is not known. Herein, using the mouse model of non-lethal P. yoelii (Py) infection, we reveal that the kinetics of blood parasitemia as well as CD4+ T follicular helper (TFH) and germinal center (GC) B cell responses are indistinguishable between PD-1-/-, PD-L1-/- and WT mice.