Understanding how nanoparticles may affect immune responses is an essential prerequisite to developing novel clinical applications. To investigate nanoparticle-dependent outcomes on immune responses, dendritic cells (DCs) were treated with model biomedical poly(vinylalcohol)-coated super-paramagnetic iron oxide nanoparticles (PVA-SPIONs). PVA-SPIONs uptake by human monocyte-derived DCs (MDDCs) was analyzed by flow cytometry (FACS) and advanced imaging techniques. Viability, activation, function, and stimulatory capacity of MDDCs were assessed by FACS and an in vitro CD4⁺ T cell assay. PVA-SPION uptake was dose-dependent, decreased by lipopolysaccharide (LPS)-induced MDDC maturation at higher particle concentrations, and was inhibited by cytochalasin D pre-treatment. PVA-SPIONs did not alter surface marker expression (CD80, CD83, CD86, myeloid/plasmacytoid DC markers) or antigen-uptake, but decreased the capacity of MDDCs to process antigen, stimulate CD4⁺ T cells, and induce cytokines. The decreased antigen processing and CD4⁺ T cell stimulation capability of MDDCs following PVA-SPION treatment suggests that MDDCs may revert to a more functionally immature state following particle exposure.

Engineered nanoparticles (NPs) offer site-specific delivery, deposition and cellular uptake due to their unique physicochemical properties and were shown to modulate immune responses. The respiratory tract with its vast surface area is an attractive target organ for innovative immunomodulatory therapeutic applications by pulmonary administration of such NPs, enabling interactions with resident antigen-presenting cells (APCs), such as dendritic cells and macrophages. Depending on the respiratory tract compartment, e.g. conducting airways, lung parenchyma, or lung draining lymph nodes, APCs extensively vary in their number, morphology, phenotype, and function. Unique characteristics and plasticity render APC populations ideal targets for inhaled specific immunomodulators. Modulation of immune responses may operate in different steps of the immune cell-antigen interaction, i.e. antigen uptake, trafficking, processing, and presentation to T cells. Meticulous analysis of the immunomodulatory potential, as well as pharmacologic and biocompatibility testing of inhalable NPs is required to develop novel strategies for the treatment of respiratory disorders such as allergic asthma. The safe-by-design and characterization of such NPs requires well coordinated interdisciplinary research uniting engineers, chemists biologists and respiratory physicians. In this review we will focus on in vivo data available to facilitate the design of nanocarrier-based strategies using NPs to modulate pulmonary immune responses.

Airway mucosal dendritic cells (AMDC) and other airway APCs continuously sample inhaled Ags and regulate the nature of any resulting T cell-mediated immune response. Although immunity develops to harmful pathogens, tolerance arises to nonpathogenic Ags in healthy individuals. This homeostasis is thought to be disrupted in allergic respiratory disorders such as allergic asthma, such that a potentially damaging Th2-biased, CD4⁺ T cell-mediated inflammatory response develops against intrinsically nonpathogenic allergens. Using a mouse model of experimental allergic airways disease (EAAD), we have investigated the functional changes occurring in AMDC and other airway APC populations during disease onset. Onset of EAAD was characterized by early and transient activation of airway CD4⁺ T cells coinciding with up-regulation of CD40 expression exclusively on CD11b⁻ AMDC. Concurrent enhanced allergen uptake and processing occurred within all airway APC populations, including B cells, macrophages, and both CD11b⁺ and CD11b⁻ AMDC subsets. Immune serum transfer into naive animals recapitulated the enhanced allergen uptake observed in airway APC populations and mediated activation of naive allergen-specific, airway CD4⁺ T cells following inhaled allergen challenge. These data suggest that the onset of EAAD is initiated by enhanced allergen capture and processing by a number of airway APC populations and that allergen-specific Igs play a role in the conversion of normally quiescent AMDC subsets into those capable of inducing airway CD4⁺ T cell activation.

Lung cancer screening (LCS) programs through low-dose Computed Tomography (LDCT) are being implemented in several countries worldwide. Radiation exposure of healthy individuals due to prolonged CT screening rounds and, eventually, the additional examinations required in case of suspicious findings may represent a concern, thus eventually reducing the participation in an LCS program. Therefore, the present review aims to assess the potential radiation risk from LDCT in this setting, providing estimates of cumulative dose and radiation-related risk in LCS in order to improve awareness for an informed and complete attendance to the program. After summarizing the results of the international trials on LCS to introduce the benefits coming from the implementation of a dedicated program, the screening-related and participant-related factors determining the radiation risk will be introduced and their burden assessed. Finally, future directions for a personalized screening program as well as technical improvements to reduce the delivered dose will be presented.

Compartmentalisation of the respiratory tract microbiota in patients with different chronic obstructive pulmonary disease (COPD) severity degrees needs to be systematically investigated. In addition, it is unknown if the inflammatory and emphysematous milieux in patients with COPD are associated with changes in the respiratory tract microbiota and host macrophage gene expression.We performed a cross-sectional study to compare non-COPD controls (n=10) to COPD patients (n=32) with different disease severity degrees. Samples (n=187) were obtained from different sites of the upper and lower respiratory tract. Microbiota analyses were performed by 16S ribosomal RNA gene sequencing and host gene expression analyses by quantitative real-time PCR of distinct markers of bronchoalveolar lavage cells.Overall, the microbial communities of severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 3/4) patients clustered significantly differently to controls and less severe COPD (GOLD 1/2) patients (permutational multivariate ANOVA (MANOVA), p=0.001). However, we could not detect significant associations between the different sampling sites in the lower airways. In addition, the chosen set of host gene expression markers significantly separated COPD GOLD 3/4 patients, and we found correlations between the composition of the microbiota and the host data.In conclusion, this study demonstrates associations between host gene expression and microbiota profiles that may influence the course of COPD.

Background: Lung function impairment persists in some patients for months after acute coronavirus disease 2019 (COVID-19). Long-term lung function, radiological features, and their association remain to be clarified. Objectives: We aimed to prospectively investigate lung function and radiological abnormalities over 12 months after severe and non-severe COVID-19. Methods: 584 patients were included in the Swiss COVID-19 lung study. We assessed lung function at 3, 6, and 12 months after acute COVID-19 and compared chest computed tomography (CT) imaging to lung functional abnormalities. Results: At 12 months, diffusion capacity for carbon monoxide (DLCOcorr) was lower after severe COVID-19 compared to non-severe COVID-19 (74.9% vs. 85.2% predicted, p < 0.001). Similarly, minimal oxygen saturation on 6-min walk test and total lung capacity were lower after severe COVID-19 (89.6% vs. 92.2%, p = 0.004, respectively, 88.2% vs. 95.1% predicted, p = 0.011). The difference for forced vital capacity (91.6% vs. 96.3% predicted, p = 0.082) was not statistically significant. Between 3 and 12 months, lung function improved in both groups and differences in DLCO between non-severe and severe COVID-19 patients decreased. In patients with chest CT scans at 12 months, we observed a correlation between radiological abnormalities and reduced lung function. While the overall extent of radiological abnormalities diminished over time, the frequency of mosaic attenuation and curvilinear patterns increased. Conclusions: In this prospective cohort study, patients who had severe COVID-19 had diminished lung function over the first year compared to those after non-severe COVID-19, albeit with a greater extent of recovery in the severe disease group.