Mouse innate-like B-1 lymphocytes promote inhaled particle-induced in vitro granuloma formation and inflammation in conjunction with macrophages

The current paradigm for explaining lung granulomatous diseases induced by inhaled particles is mainly based on macrophages. This mechanism is now challenging because B lymphocytes also infiltrate injured tissue, and the deficiency in B lymphocytes is associated with limited lung granulomas in silica-treated mice. Here, we investigated how B lymphocytes respond to micro- and nanoparticles by combining in vivo and in vitro mouse models. We first demonstrated that innate-like B-1 lymphocytes (not conventional B-2 lymphocytes or plasma cells) specifically accumulated during granuloma formation in mice instilled with crystalline silica (DQ12, 2.5 mg/mouse) and carbon nanotubes (CNT Mitsui, 0.2 mg/mouse). In comparison to macrophages, peritoneal B-1 lymphocytes purified from naïve mice were resistant to the pyroptotic activity of reactive particles (up to 1 mg/mL) but clustered to establish in vitro cell/particle aggregates. Mouse B-1 lymphocytes (not B-2 lymphocytes) in coculture with macrophages and CNT (0.1 µg/mL) organized three-dimensional spheroid structures in Matrigel and stimulated the release of TIMP-1. Furthermore, purified B-1 lymphocytes are sensitive to nanosilica toxicity through radical generation in culture. Nanosilica-exposed B-1 lymphocytes released proinflammatory cytokines and alarmins. In conclusion, our data indicate that in addition to macrophages, B-1 lymphocytes participate in micrometric particle-induced granuloma formation and display inflammatory functions in response to nanoparticles.

Healthy lungs maintain a young and energetic body

In general, life is only possible in the presence of oxygen in a form that can be easily absorbed by the body. In the case of humans, the lungs have as their main task the provision of the oxygen necessary for the body to carry out daily activities. The lung is a paired organ located in the chest cavity, a fibro-elastic organ capable of altering your volume during breathing (inspire and expire). The weight of a lung varies between 800 and 1,000 grams, of which more than 50% is blood. The air reaches the lungs through a pipeline system consisting of Nazo-pharynx, larynx, trachea, bronchi, and bronchiole. The role of the piping system is to heat and dampen the air or to capture and remove foreign inhaled particles. The channel system decreases in diameter after each branch - from the trachea and the large bronchi to the bronchiole with a diameter of less than one millimeter. The lung consists of over 30 different cell types. Trachea and large bronchi are taped by a mucous layer containing multiple cell types: ciliary cells - provides mucus movement, caliciform cells - secretes mucus, basal cells - plays a role in regeneration and neuro-ectodermic cells - ensures the secretory function of the lungs. In the chorion (the deep layer beneath the mucosa) there are cells involved in the defense processes - lymphocytes, mast cells, eosinophils or neutrophils.

Shape matters—the interaction of gold nanoparticles with model lung surfactant monolayers

The lung surfactant monolayer (LSM) forms the main biological barrier for any inhaled particles to enter our bloodstream, including gold nanoparticles (AuNPs) present as air pollutants and under investigation for use in biomedical applications. Understanding the interaction of AuNPs with lung surfactant can assist in understanding how AuNPs enter our lungs. In this study, we use coarse-grained molecular dynamics simulations to investigate the effect of four different shape D AuNPs (spherical, box, icosahedron and rod) on the structure and dynamics of a model LSM, with a particular focus on differences resulting from the shape of the AuNP. Monolayer-AuNP systems were simulated in two different states: the compressed state and the expanded state, representing inhalation and exhalation conditions, respectively. Our results indicate that the compressed state is more affected by the presence of the AuNPs than the expanded state. Our results show that in the compressed state, the AuNPs prevent the monolayer from reaching the close to zero surface tension required for normal exhalation. In the compressed state, all four nanoparticles (NPs) reduce the lipid order parameters and cause a thinning of the monolayer where the particles drag surfactant molecules into the water phase. Comparing the different properties shows no trend concerning which shape has the biggest effect on the monolayer, as shape-dependent effects vary among the different properties. Insights from this study might assist future work of how AuNP shapes affect the LSM during inhalation or exhalation conditions.

Quantitative modeling of the impact of facemasks and associated leakage on the airborne transmission of SARS-CoV-2

The ongoing worldwide outbreak of COVID-19 has set personal protective equipment in the spotlight. A significant number of countries impose the use of facemasks in public spaces and encourage it in the private sphere. Even in countries where relatively high vaccination rates are achieved at present, breakthrough infections have been frequently reported and usage of facemasks in certain settings has been recommended again. Alternative solutions, including community masks fabricated using various materials, such as cotton or jersey, have emerged alongside facemasks following long-established standards (e.g., EN 149, EN 14683). In the present work, we present a computational model to calculate the ability of different types of facemasks to reduce the exposure to virus-laden respiratory particles, with a focus on the relative importance of the filtration properties and the fitting on the wearer’s face. The model considers the facemask and the associated leakage, the transport of respiratory particles and their accumulation around the emitter, as well as the fraction of the inhaled particles deposited in the respiratory system. Different levels of leakages are considered to represent the diversity of fittings likely to be found among a population of non-trained users. The leakage prevails over the filtration performance of a facemask in determining the exposure level, and the ability of a face protection to limit leakages needs to be taken into account to accurately estimate the provided protection. Filtering facepieces (FFP) provide a better protection efficiency than surgical and community masks due to their higher filtration efficiency and their ability to provide a better fit and thus reduce the leakages. However, an improperly-fitted FFP mask loses a critical fraction of its protection efficiency, which may drop below the protection level provided by properly-worn surgical and community masks.

Relationship between Occupational Exposure to Airborne Nanoparticles, Nanoparticle Lung Burden and Lung Diseases

The biomonitoring of nanoparticles in patients’ broncho-alveolar lavages (BAL) could allow getting insights into the role of inhaled biopersistent nanoparticles in the etiology/development of some respiratory diseases. Our objective was to investigate the relationship between the biomonitoring of nanoparticles in BAL, interstitial lung diseases and occupational exposure to these particles released unintentionally. We analyzed data from a cohort of 100 patients suffering from lung diseases (NanoPI clinical trial, ClinicalTrials.gov Identifier: NCT02549248) and observed that most of the patients showed a high probability of exposure to airborne unintentionally released nanoparticles (>50%), suggesting a potential role of inhaled nanoparticles in lung physiopathology. Depending on the respiratory disease, the amount of patients likely exposed to unintentionally released nanoparticles was variable (e.g., from 88% for idiopathic pulmonary fibrosis to 54% for sarcoidosis). These findings are consistent with the previously performed mineralogical analyses of BAL samples that suggested (i) a role of titanium nanoparticles in idiopathic pulmonary fibrosis and (ii) a contribution of silica submicron particles to sarcoidosis. Further investigations are necessary to draw firm conclusions but these first results strengthen the array of presumptions on the contribution of some inhaled particles (from nano to submicron size) to some idiopathic lung diseases.

Signaling Control of Mucociliary Epithelia: Stem Cells, Cell Fates, and the Plasticity of Cell Identity in Development and Disease

Mucociliary epithelia are composed of multiciliated, secretory, and stem cells and line various organs in vertebrates such as the respiratory tract. By means of mucociliary clearance, those epithelia provide a first line of defense against inhaled particles and pathogens. Mucociliary clearance relies on the correct composition of cell types, that is, the proper balance of ciliated and secretory cells. A failure to generate and to maintain correct cell type composition and function results in impaired clearance and high risk to infections, such as in congenital diseases (e.g., ciliopathies) as well as in acquired diseases, including asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). While it remains incompletely resolved how precisely cell types are specified and maintained in development and disease, many studies have revealed important mechanisms regarding the signaling control in mucociliary cell types in various species. Those studies not only provided insights into the signaling contribution to organ development and regeneration but also highlighted the remarkable plasticity of cell identity encountered in mucociliary maintenance, including frequent trans-differentiation events during homeostasis and specifically in disease. This review will summarize major findings and provide perspectives regarding the future of mucociliary research and the treatment of chronic airway diseases associated with tissue remodeling.

Engineered Lego®-like microphysiological models of the human airway clearance phenomena

Mucociliary clearance is a crucial event that supports the elimination of inhaled particles, bacteria, pollution and hazardous agents from the human airways, and it also limits the diffusion of aerosolized drugs into the airway epithelium. In spite of its relevance, few in vitro models sufficiently address the cumulative effect of the steric and interactive barrier function of mucus on the one hand, and the dynamic mucus transport imposed by ciliary mucus propulsion on the other hand. Here, ad hoc mucus models of physiological and pathological mucus are combined with magnetic artificial cilia to model mucociliary transport in both physiological and pathological states. The Lego®-like concept adopted, in this study, enables the development of mucociliary clearance models with high versatility, since these can be easily modified to reproduce phenomena characteristic of healthy and diseased human airways, while allowing to determine the effect of each parameter and/or structure separately on the overall mucociliary transport. These Lego®-like airway models can be available off-the-shelf because they are exclusively made of readily available materials, thus ensuring reproducibility across different laboratories.

Experimental Efficacy of the Face Shield and the Mask against Emitted and Potentially Received Particles

There is currently not sufficient evidence to support the effectiveness of face shields for source control. In order to evaluate the comparative barrier performance effect of face masks and face shields, we used an aerosol generator and a particle counter to evaluate the performance of the various devices in comparable situations. We tested different configurations in an experimental setup with manikin heads wearing masks (surgical type I), face shields (22.5 cm high with overhang under the chin of 7 cm and circumference of 35 cm) on an emitter or a receiver manikin head, or both. The manikins were face to face, 25 cm apart, with an intense particle emission (52.5 L/min) for 30 s. The particle counter calculated the total cumulative particles aspirated on a volume of 1.416 L In our experimental conditions, when the receiver alone wore a protection, the face shield was more effective (reduction factor = 54.8%), while reduction was lower with a mask (reduction factor = 21.8%) (p = 0.002). The wearing of a protective device by the emitter alone reduced the level of received particles by 96.8% for both the mask and face shield (p = NS). When both the emitter and receiver manikin heads wore a face shield, the protection allowed for better results in our experimental conditions: 98% reduction for the face shields versus 97.3% for the masks (p = 0.01). Face shields offered an even better barrier effect than the mask against small inhaled particles (<0.3 µm–0.3 to 0.5 µm–0.5 to 1 µm) in all configurations. Therefore, it would be interesting to include face shields as used in our experimental study as part of strategies to reduce transmission within the community setting.