CARD8 polymorphisms among bacterial meningitis patients in North-West Ethiopia.

Background: The severity of infectious disease outcomes is dependent on the virulence factors of the pathogen and the host immune response. CARD8 is a major regulator of the innate immune proinflammatory response and has been suggested to modulate the host response to common inflammatory diseases. In the present study, the C10X genetic polymorphism in the CARD8 gene was investigated in relation to bacterial meningitis.

Exposing kinetic disparities between inflammasome readouts using time-resolved analysis.

The NLRP3 inflammasome is an intracellular multiprotein complex described to be involved in both an effective host response to infectious agents and various diseases. Investigation into the NLRP3 inflammasome has been extensive in the past two decades, and often revolves around the analysis of a few specific readouts, including ASC-speck formation, caspase-1 cleavage or activation, and cleavage and release of IL-1β and/or IL-18. Quantification of these readouts is commonly undertaken as an endpoint analysis, where the presence of each positive outcome is assessed independently of the others.

Diverse proinflammatory response in pharyngeal epithelial cells upon interaction with Neisseria meningitidis carriage and invasive isolates.

Background: Invasive meningococcal disease (IMD), including sepsis and meningitis, can develop when Neisseria meningitidis bacteria breach the barrier and gain access to the circulation. While IMD is a rare outcome of bacterial exposure, colonization of the oropharynx is present in approximately 10% of the human population. This asymptomatic carriage can be long or short term, and it is unknown which determining factors regulate bacterial colonization.

Immunotoxic, genotoxic, and endocrine disrupting impacts of polyamide microplastic particles and chemicals.

Due to their exceptional properties and cost effectiveness, polyamides or nylons have emerged as widely used materials, revolutionizing diverse industries, including industrial 3D printing or additive manufacturing (AM). Powder-based AM technologies employ tonnes of polyamide microplastics to produce complex components every year. However, the lack of comprehensive toxicity assessment of particulate polyamides and polyamide-associated chemicals, especially in the light of the global microplastics crisis, calls for urgent action.

Mathematical models disentangle the role of IL-10 feedbacks in human monocytes upon proinflammatory activation.

Inflammation is one of the vital mechanisms through which the immune system responds to harmful stimuli. During inflammation, proinflammatory and anti-inflammatory cytokines interplay to orchestrate fine-tuned and dynamic immune responses. The cytokine interplay governs switches in the inflammatory response and dictates the propagation and development of the inflammatory response.

NLRP3 inflammasome as a sensor of micro- and nanoplastics immunotoxicity.

Micro- and nanoplastics (MNPs) are emerging pollutants with scarcely investigated effects on human innate immunity. If they follow a similar course of action as other, more thoroughly investigated particulates, MNPs may penetrate epithelial barriers, potentially triggering a cascade of signaling events leading to cell damage and inflammation. Inflammasomes are intracellular multiprotein complexes and stimulus-induced sensors critical for mounting inflammatory responses upon recognition of pathogen- or damage-associated molecular patterns.

Occupational quartz and particle exposure affect systemic levels of inflammatory markers related to inflammasome activation and cardiovascular disease.

Background: The inflammatory responses are central components of diseases associated with particulate matter (PM) exposure, including systemic diseases such as cardiovascular diseases (CVDs). The aim of this study was to determine if exposure to PM, including respirable dust or quartz in the iron foundry environment mediates systemic inflammatory responses, focusing on the NLRP3 inflammasome and novel or established inflammatory markers of CVDs.

Methods: The exposure to PM, including respirable dust, metals and quartz were determined in 40 foundry workers at two separate occasions per worker.

Prevalence and persistence of carriage in Swedish university students.

The bacterium causes life-threatening disease worldwide, typically with a clinical presentation of sepsis or meningitis, but can be carried asymptomatically as part of the normal human oropharyngeal microbiota. The aim of this study was to examine carriage with regard to prevalence, risk factors for carriage, distribution of meningococcal lineages and persistence of meningococcal carriage. Throat samples and data from a self-reported questionnaire were obtained from 2744 university students (median age: 23 years) at a university in Sweden on four occasions during a 12-month period.

A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles.

Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry.

Particle Safety Assessment in Additive Manufacturing: From Exposure Risks to Advanced Toxicology Testing.

Additive manufacturing (AM) or industrial three-dimensional (3D) printing drives a new spectrum of design and production possibilities; pushing the boundaries both in the application by production of sophisticated products as well as the development of next-generation materials. AM technologies apply a diversity of feedstocks, including plastic, metallic, and ceramic particle powders with distinct size, shape, and surface chemistry. In addition, powders are often reused, which may change the particles' physicochemical properties and by that alter their toxic potential.

Cytokine responses to LPS in reprogrammed monocytes are associated with the transcription factor PU.1.

Myeloid-derived suppressor cells (MDSCs) are functionally immunosuppressive cells that arise and expand during extensive inflammatory conditions by increased hematopoietic output or reprogramming of immune cells. In sepsis, an increase of circulating MDSCs is associated with adverse outcomes, but unique traits that can be used to identify increased activity of MDSCs are lacking. By using endotoxin tolerance as a model of sepsis-induced monocytic MDSCs (M-MDSC-like cells), this study aims to identify the mediator and transcriptional regulator profile associated with M-MDSC activity.

Toxicity evaluation of particles formed during 3D-printing: Cytotoxic, genotoxic, and inflammatory response in lung and macrophage models.

Additive manufacturing (AM) or "3D-printing" is a ground-breaking technology that enables the production of complex 3D parts. Its rapid growth calls for immediate toxicological investigations of possible human exposures in order to estimate occupational health risks. Several laser-based powder bed fusion AM techniques are available of which many use metal powder in the micrometer range as feedstock.

Effects on white blood cell counts and the NLRP3 inflammasome due to dust and cobalt exposure in the hard metal industry.

Introduction: In light of potential negative health effects of cobalt exposure, a characterization of inflammatory mechanisms in exposed individuals is warranted. The current study investigated cobalt exposure in the Swedish hard metal industry and its relationship to inflammatory markers, including NLRP3 inflammasome activation and white blood cell (WBC) counts.

Materials And Methods: Inhalable cobalt and dust exposures, and systemic cobalt levels, were determined for 72 workers in the hard metal industry and linear regression models were applied to correlate exposure to markers of inflammasome activation and WBC counts.

Dermal exposure to cobalt studied in keratinocytes - effects of cobalt exposure on inflammasome activated cytokines, and mRNA response.

Background: Cobalt is a dermal sensitizer, and keratinocytes respond to cobalt exposure by releasing proinflammatory mediators, regulating the immune response.

Objective: To determine the effect of cobalt on the inflammasome associated cytokine- and gene expression in cultured human keratinocytes (HaCaT). Cultivation in low- or high calcium conditions model separate differentiation states of keratinocytes in the skin.

Inflammatory and coagulatory markers and exposure to different size fractions of particle mass, number and surface area air concentrations in the Swedish hard metal industry, in particular to cobalt.

Purpose: To study the relationship between inhalation of airborne particles and cobalt in the Swedish hard metal industry and markers of inflammation and coagulation in blood.

Methods: Personal sampling of inhalable cobalt and dust were performed for subjects in two Swedish hard metal plants. Stationary measurements were used to study concentrations of inhalable, respirable, and total dust and cobalt, PM and PM, the particle surface area and the particle number concentrations.

Dose- and time-dependent changes in viability and IL-6, CXCL8 and CCL2 production by HaCaT-cells exposed to cobalt. Effects of high and low calcium growth conditions.

Background: Sensitization requires exposure to an allergen with subsequent production of a "danger "signal. In the skin, keratinocytes are the main producers of these signals.

Objective: To compare dose- and time-effects of cobalt on the viability of and cytokine release from HaCaT cells cultured at low or high calcium.

Activation of NLRP3 by uropathogenic Escherichia coli is associated with IL-1β release and regulation of antimicrobial properties in human neutrophils.

The NLRP3 inflammasome and IL-1β have recently been linked to the severity of uropathogenic Escherichia coli (UPEC)-mediated urinary tract infection (UTI). However, not much is known about the contribution of NLRP3 to the antimicrobial properties of neutrophils and the release of IL-1β during UPEC infection. The purpose of this study was to elucidate the mechanisms behind UPEC-induced IL-1β release from human neutrophils, and to investigate the contribution of the NLRP3 inflammasome in neutrophil-mediated inhibition of UPEC growth.

Mechanisms of a Sustained Anti-inflammatory Drug Response in Alveolar Macrophages Unraveled with Mathematical Modeling.

Both initiation and suppression of inflammation are hallmarks of the immune response. If not balanced, the inflammation may cause extensive tissue damage, which is associated with common diseases, e.g.

Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1 and Interleukin-18 from Human Monocytes.

Inflammasomes cleave and activate interleukin- (IL-) 1 and IL-18 which have both shared and unique biological functions. IL-1 is an important mediator of the acute phase response to infections and tissue damage, whereas IL-18 takes part in activation and tailoring of the adaptive immune response. While IL-1 has served as the prototypic indicator of inflammasome activation, few studies have compared the potential differences in IL-1 and IL-18 production during inflammasome activation.

Respiratory Health and Inflammatory Markers-Exposure to Cobalt in the Swedish Hard Metal Industry.

Objective: To study the relationship between inhalable dust and cobalt, and respiratory symptoms, lung function, exhaled nitric oxide in expired air, and CC16 in the Swedish hard metal industry.

Methods: Personal sampling of inhalable dust and cobalt, and medical examination including blood sampling was performed for 72 workers. Exposure-response relationships were determined using logistic, linear, and mixed-model analysis.

Quartz Dust Exposure Affects NLRP3 Inflammasome Activation and Plasma Levels of IL-18 and IL-1Ra in Iron Foundry Workers.

Purpose: To study the association between inhalation of particulate matter or quartz in Swedish iron foundries and the effects on NLRP3 inflammasome activation.

Methods: Particle exposure measurements were performed during an eight-hour work day for 85 foundry workers at three Swedish iron foundries. Personal sampling was used for measurement of respirable quartz and dust and stationary measurements to obtain exposure measurements for inhalable dust and PM.

Respiratory health and inflammatory markers - Exposure to respirable dust and quartz and chemical binders in Swedish iron foundries.

Purpose: To study the relationship between respirable dust, quartz and chemical binders in Swedish iron foundries and respiratory symptoms, lung function (as forced expiratory volume FEV1 and vital capacity FVC), fraction of exhaled nitric oxide (FENO) and levels of club cell secretory protein 16 (CC16) and CRP.

Methods: Personal sampling of respirable dust and quartz was performed for 85 subjects in three Swedish iron foundries. Full shift sampling and examination were performed on the second or third day of a working week after a work free weekend, with additional sampling on the fourth or fifth day.

-Induced Caspase-1 Activation in Human Innate Immune Cells Is LOS-Dependent.

Meningococcal disease such as sepsis and meningitidis is hallmarked by an excessive inflammatory response. The causative agent, , expresses the endotoxin lipooligosaccharide (LOS) that is responsible for activation of immune cells and the release of proinflammatory cytokines. One of the most potent proinflammatory cytokines, interleukin-1 (IL-1), is activated following caspase-1 activity in the intracellular multiprotein complex called inflammasome.

Inflammatory and coagulatory markers and exposure to different size fractions of particle mass, number and surface area air concentrations in Swedish iron foundries, in particular respirable quartz.

Purpose: To study the relationship between inhalation of airborne particles and quartz in Swedish iron foundries and markers of inflammation and coagulation in blood.

Methods: Personal sampling of respirable dust and quartz was performed for 85 subjects in three Swedish iron foundries. Stationary measurements were used to study the concentrations of respirable dust and quartz, inhalable and total dust, PM10 and PM2.