RAGE engagement by SARS-CoV-2 enables monocyte infection and underlies COVID-19 severity.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has fueled the COVID-19 pandemic with its enduring medical and socioeconomic challenges because of subsequent waves and long-term consequences of great concern. Here, we chart the molecular basis of COVID-19 pathogenesis by analyzing patients' immune responses at single-cell resolution across disease course and severity. This approach confirms cell subpopulation-specific dysregulation in COVID-19 across disease course and severity and identifies a severity-associated activation of the receptor for advanced glycation endproducts (RAGE) pathway in monocytes.

High-Throughput Microscopy Analysis of Mitochondrial Membrane Potential in 2D and 3D Models.

Recent proteomic, metabolomic, and transcriptomic studies have highlighted a connection between changes in mitochondria physiology and cellular pathophysiological mechanisms. Secondary assays to assess the function of these organelles appear fundamental to validate these -omics findings. Although mitochondrial membrane potential is widely recognized as an indicator of mitochondrial activity, high-content imaging-based approaches coupled to multiparametric to measure it have not been established yet.

Atypical CXCL12 signaling enhances neutrophil migration by modulating nuclear deformability.

To reach inflamed tissues from the circulation, neutrophils must overcome physical constraints imposed by the tissue architecture, such as the endothelial barrier or the three-dimensional (3D) interstitial space. In these microenvironments, neutrophils are forced to migrate through spaces smaller than their own diameter. One of the main challenges for cell passage through narrow gaps is the deformation of the nucleus, the largest and stiffest organelle in cells.

OPA1 drives macrophage metabolism and functional commitment via p65 signaling.

Macrophages are essential players for the host response against pathogens, regulation of inflammation and tissue regeneration. The wide range of macrophage functions rely on their heterogeneity and plasticity that enable a dynamic adaptation of their responses according to the surrounding environmental cues. Recent studies suggest that metabolism provides synergistic support for macrophage activation and elicitation of desirable immune responses; however, the metabolic pathways orchestrating macrophage activation are still under scrutiny.

IL1β Promotes TMPRSS2 Expression and SARS-CoV-2 Cell Entry Through the p38 MAPK-GATA2 Axis.

After the outburst of the SARS-CoV-2 pandemic, a worldwide research effort has led to the uncovering of many aspects of the COVID-19, among which we can count the outstanding role played by inflammatory cytokine milieu in the disease progression. Despite that, molecular mechanisms that regulate SARS-CoV-2 pathogenesis are still almost unidentified. In this study, we investigated whether the pro-inflammatory milieu of the host affects the susceptibility of SARS-CoV-2 infection by modulating and expression.

The J2-Immortalized Murine Macrophage Cell Line Displays Phenotypical and Metabolic Features of Primary BMDMs in Their M1 and M2 Polarization State.

Macrophages are immune cells that are important for the development of the defensive front line of the innate immune system. Following signal recognition, macrophages undergo activation toward specific functional states, consisting not only in the acquisition of specific features but also of peculiar metabolic programs associated with each function. For these reasons, macrophages are often isolated from mice to perform cellular assays to study the mechanisms mediating immune cell activation.

The dominant-negative mitochondrial calcium uniporter subunit MCUb drives macrophage polarization during skeletal muscle regeneration.

Damaged skeletal muscle can regenerate because of the coordinated action of immune cells with muscle stem cells, called satellite cells. Proinflammatory macrophages infiltrate skeletal muscle soon after injury to sustain the proliferation of satellite cells. These macrophages later acquire the anti-inflammatory phenotype and promote the differentiation and fusion of satellite cells.

Age-severity matched cytokine profiling reveals specific signatures in Covid-19 patients.

A global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcomes, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell exhaustion, and the increased levels of inflammatory mediators have been described in COVID-19 patients, in particular in severe cases.

Innate immunity ascertained from blood and tracheal aspirates of preterm newborn provides new clues for assessing bronchopulmonary dysplasia.

Aim: The study aimed to establish how granulocytes, monocytes and macrophages contribute to the development of bronchopulmonary dysplasia (BPD).

Materials And Methods: Study A: samples of blood and tracheal aspirates (TAs) collected from preterm newborn infants during the first 3 days of life were investigated by flow cytometry, and testing for white blood cells (WBCs), neutrophils and neutrophil extracellular traps (NETs). Maternal blood samples were also collected.

The Metabolic Signature of Macrophage Responses.

Macrophages are a heterogeneous population of immune cells playing several and diverse functions in homeostatic and immune responses. The broad spectrum of macrophage functions depends on both heterogeneity and plasticity of these cells, which are highly specialized in sensing the microenvironment and modify their properties accordingly. Although it is clear that macrophage phenotypes are difficult to categorize and should be seen as plastic and adaptable, they can be simplified into two extremes: a pro-inflammatory (M1) and an anti-inflammatory/pro-resolving (M2) profile.

Intercellular Calcium Signaling Induced by ATP Potentiates Macrophage Phagocytosis.

Extracellular ATP is a signaling molecule exploited by the immune cells for both autocrine regulation and paracrine communication. By performing live calcium imaging experiments, we show that triggered mouse macrophages are able to propagate calcium signals to resting bystander cells by releasing ATP. ATP-based intercellular communication is mediated by P2X4 and P2X7 receptors and is a feature of pro-inflammatory macrophages.

Affects the Antigen Presentation Activity of Macrophages Modulating the Expression of the Immune Receptor CD300E through miR-4270.

(Hp) is a Gram-negative bacterium that infects the human gastric mucosa, leading to chronic inflammation. If not eradicated with antibiotic treatment, the bacterium persists in the human stomach for decades increasing the risk to develop chronic gastritis, gastroduodenal ulcer, and gastric adenocarcinoma. The lifelong persistence of Hp in the human stomach suggests that the host response fails to clear the infection.

A pH-sensitive stearoyl-PEG-poly(methacryloyl sulfadimethoxine)-decorated liposome system for protein delivery: An application for bladder cancer treatment.

Stealth pH-responsive liposomes for the delivery of therapeutic proteins to the bladder epithelium were prepared using methoxy-poly(ethylene glycol)5kDa-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG5kDa-DSPE) and stearoyl-poly(ethylene glycol)-poly(methacryloyl sulfadimethoxine) copolymer (stearoyl-PEG-polySDM), which possesses an apparent pKa of 7.2. Liposomes of 0.

Evaluation of the Efficacy of the H. pylori Protein HP-NAP as a Therapeutic Tool for Treatment of Bladder Cancer in an Orthotopic Murine Model.

Bladder cancer is one of the most common malignancies of the urogenital tract. Intravesical injection of Bacillus Calmette-Guérin (BCG) is the gold standard treatment for the high-grade non-muscle invasive bladder cancer (NMIBC). However, since the treatment-related side effects are relevant, newer biological response modifiers with a better benefit/side effects ratio are needed.

Cytokine BAFF released by Helicobacter pylori-infected macrophages triggers the Th17 response in human chronic gastritis.

BAFF is a crucial cytokine that affects the activity of both innate and adaptive immune cells. It promotes the expansion of Th17 cells in autoimmune disorders. With this study, we investigated the BAFF/Th17 responses in Helicobacter pylori-induced gastritis in humans.

Helicobacter pylori secreted peptidyl prolyl cis, trans-isomerase drives Th17 inflammation in gastric adenocarcinoma.

Helicobacter pylori infection is characterized by an inflammatory infiltrate, consisting mainly of neutrophils and T cells. This study was undertaken to evaluate the type of gastric T cell response elicited by the secreted peptidyl prolyl cis, trans-isomerase of H. pylori (HP0175) in patients with distal gastric adenocarcinoma.

[Therapy for non-muscle invasive bladder cancer: HP-NAP].

Purpose: Patients with non-muscle invasive bladder cancer recurrence after 2 induction courses of BCG are eligible for radical cystectomy. So, in the last years research to discover new drugs for the management of non-muscle invasive bladder cancer recurrence after failure of first and second line therapy is ongoing. In accordance to the results obtained with BCG, whose mechanism depends on the induction of the T helper 1 (TH1) immune response, we investigated the activity of a Toll-like receptor (TLR) 2 ligand, named Helicobacter Pylori Neutrophil Activating Protein (HP-NAP), that we recently demonstrated being able of enhancing the differentiation of Th1 cells, both in vitro and in vivo, because of its ability to create an IL-12 enriched milieu.

Chlamydophila pneumoniae phospholipase D (CpPLD) drives Th17 inflammation in human atherosclerosis.

Phospholipases are produced from bacterial pathogens causing very different diseases. One of the most intriguing aspects of phospholipases is their potential to interfere with cellular signaling cascades and to modulate the host-immune response. Here, we investigated the role of the innate and acquired immune responses elicited by Chlamydophila pneumoniae phospholipase D (CpPLD) in the pathogenesis of atherosclerosis.

HP-NAP inhibits the growth of bladder cancer in mice by activating a cytotoxic Th1 response.

Intravesical Bacillus Calmette-Guérin (BCG) is the gold standard treatment for intermediate and high-risk non-muscle-invasive bladder cancer. BCG therapy is the most successful example of immunotherapy in cancer. Unfortunately, the treatment-related side effects are still relevant.

Tumor-associated macrophages as major source of APRIL in gastric MALT lymphoma.

Lymphoid hyperplasia of gastric mucosa associated with Helicobacter pylori (HP) infection represents a preneoplastic condition of the mucosa associated lymphoid tissue (MALT), which may evolve to a B-cell lymphoma. While it is well established that the initial neoplastic proliferation of B cells is antigen-driven and dependent on the helper activity of HP-specific T cells, it needs to be elucidated which cytokine or soluble factor(s) promote B-cell activation and lymphomagenesis. Herein, we originally report that gastric MALT lymphoma express high levels of a proliferation inducing ligand (APRIL), a novel cytokine crucial in sustaining B-cell proliferation.