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In recent years, evidence of the synergistic effects of pollen and viruses on respiratory health has begun to accumulate. Pollen exposure is a known risk factor for the incidence and severity of respiratory viral infections. However, recent evidence suggests that pollen exposure may also inhibit or weaken viral infections. A comprehensive summary has not been made and a consensus on the synergistic health effects has not been reached. It is highly possible that climate change will increase the significance of pollen exposure as a cause of respiratory problems and, at the same time, affect the risk of infectious disease outbreaks. It is important to accurately assess how these two factors affect human health separately and concurrently. In this review article, for the first time, the data from previous studies are combined and reviewed and potential research gaps concerning the synergistic effects of pollen and viral exposure are identified.

The adverse effects of air pollutants on the respiratory and cardiovascular systems are unquestionable. However, in recent years, indications of effects beyond these organ systems have become more evident. Traffic-related air pollution has been linked with neurological diseases, exacerbated cognitive dysfunction, and Alzheimer’s disease. However, the exact air pollutant compositions and exposure scenarios leading to these adverse health effects are not known. Although several components of air pollution may be at play, recent experimental studies point to a key role of ultrafine particles (UFPs). While the importance of UFPs has been recognized, almost nothing is known about the smallest fraction of UFPs, and only >23 nm emissions are regulated in the EU. Moreover, the role of the semivolatile fraction of the emissions has been neglected. The Transport-Derived Ultrafines and the Brain Effects (TUBE) project will increase knowledge on harmful ultrafine air pollutants, as well as semivolatile compounds related to adverse health effects. By including all the major current combustion and emission control technologies, the TUBE project aims to provide new information on the adverse health effects of current traffic, as well as information for decision makers to develop more effective emission legislation. Most importantly, the TUBE project will include adverse health effects beyond the respiratory system; TUBE will assess how air pollution affects the brain and how air pollution particles might be removed from the brain. The purpose of this report is to describe the TUBE project, its background, and its goals. publishedVersion

Solid fuel usage in residential heating and cooking is one of the largest sources of ambient and indoor air particulate matter, which causes adverse effects on the health of millions of peoples worldwide. Emissions from solid fuel combustion, such as biomass or coal, are detrimental to health, but toxicological responses are largely unknown. In the present study, we compared the toxicological responses regarding cytotoxicity, inflammation and genotoxicity of spruce (SPR) and brown coal briquette (BCB) combustion aerosols on human alveolar epithelial cells (A549) as well as a coculture of A549 and differentiated human monocytic cells (THP-1) into macrophages exposed at the air-liquid interface (ALI). We included both the high emissions from the first hour and moderate emissions from the third hour of the batch combustion experiment in one ALI system, whereas, in the second ALI system, we exposed the cells during the whole 4-hour combustion experiment, including all combustion phases. Physico-chemical properties of the combustion aerosol were analysed both online and offline. Both SPR and BCB combustion aerosols caused mild cytotoxic but notable genotoxic effects in co-cultured A549 cells after one-hour exposure. Inflammatory response analysis revealed BCB combustion aerosols to cause a mild increase in CXCL1 and CXCL8 levels, but in the case of SPR combustion aerosol, a decrease compared to control was observed.

The health risks of air pollutants and ambient particulate matter (PM) are widely known. PM composition and toxicity have shown substantial spatiotemporal variability. Yet, the connections between PM composition and toxicological and health effects are vaguely understood. This is a crucial gap in knowledge that needs to be addressed in order to establish air quality guidelines and limit values that consider the chemical composition of PM instead of the current assumption of equal toxicity per inhaled dose. Here, we demonstrate further evidence for varying toxicological effects of urban PM at equal mass concentrations, and estimate how PM composition and emission source characteristics influenced this variation. We exposed a co-culture model mimicking alveolar epithelial cells and macrophages with size-segregated urban ambient PM collected before, during, and after the Nanjing Youth Olympic Games 2014. We measured the release of a set of cytokines, cell cycle alterations, and genotoxicity, and assessed the spatiotemporal variations in these responses by factorial multiple regression analysis. Additionally, we investigated how a previously identified set of emission sources and chemical components affected these variations by mixed model analysis. PM-exposure induced cytokine signaling, most notably by inducing dose-dependent increases of macrophage-regulating GM-CSF and proinflammatory TNFα, IL-6, and IL-1β concentrations, modest dose-dependent increase for cytoprotective VEGF-A, but very low to no responses for anti-inflammatory IL-10 and immunoregulatory IFNγ, respectively. We observed substantial differences in proinflammatory cytokine production depending on PM sampling period, location, and time of day. The proinflammatory response correlated positively with cell cycle arrest in G1/G0 phase and loss of cellular metabolic activity. Furthermore, PM

Additional file 8 Figure S4. Viability (A), Comet assay (B) and IL-8 secretion (C) of A549 control cells after exposed one hour at incubator with CO2, incubator without CO2 or Tox-ALI to clean air. Each bar shows mean ± SEM, n = 3.

Additional file 4 Figure S2. Size of the particles measured by SMPS per day to day. The geometric mean diameters are shown with the solid lines, while GSDs are represented with dashed lines. (average of 3 experiments)

Additional file 7 Table S3. Inorganic elements from spruce and pine combustion emissions. Organic compounds were sampled over 4-h exposure. Concentrations are calculated as averages from three test cycles ± standard deviation.

Additional file 9 Table S4. Top 5 significant ingenuity canonical pathways of spruce aerosol exposure.

Additional file 5 Figure S3. Size of the particles measured by SMPS. The geometric mean diameters (a) and mass median diameters (b) are shown with the solid lines, while GSDs are represented with dashed lines. Average of 3 experiments.

Additional file 11 Figure S5. Area under curve (AUC) calculated from exposed A549 cells from three different timepoints of H2DCFDA measurements. Each bar shows mean ± SEM, n = 3.

Background Studies conducted in farm environments suggest that diverse microbial exposure promotes children's lung health. The underlying mechanisms are unclear, and the development of asthma-preventive strategies has been delayed. More comprehensive investigation of the environment-induced immunoregulation is required for better understanding of asthma pathogenesis and prevention. Exposure to air pollution, including particulate matter (PM), is a risk factor for asthma, thus providing an excellent counterpoint for the farm-effect research. Lack of comparable data, however, complicates interpretation of the existing information. We aimed to explore the immunoregulatory effects of cattle farm dust (protective, Finland) and urban air PM (high-risk, China) for the first time using identical research methods. Methods We stimulated PBMCs of 4-year-old children (N = 18) with farm dust and size-segregated PM and assessed the expression of immune receptors CD80 and ILT4 on dendritic cells and monocytes as well as cytokine production of PBMCs. Environmental samples were analysed for their composition. Results Farm dust increased the percentage of cells expressing CD80 and the cytokine production of children's immune cells, whereas PM inhibited the expression of important receptors and the production of soluble mediators. Although PM samples induced parallel immune reactions, the size-fraction determined the strength of the effects. Conclusions Our study demonstrates the significance of using the same research framework when disentangling shared and distinctive immune pathways operating in different environments. Observed stimulatory effects of farm dust and inhibitory effects of PM could shape responses towards respiratory pathogens and allergens, and partly explain differences in asthma prevalence between studied environments.

Exposure to farm environment has been shown to both protect from allergic diseases and increase the risk of respiratory syndromes. Mechanisms have been previously investigated by using farm dust extracts or specific components of dust. The use of authentic farm dust would better reflect the natural exposure. The aim of our study was to highlight the importance of proper assessment of the cow stable dust characteristics before conducting further investigations. For this purpose, we characterized microbiome and size distribution of unprocessed cow stable dust and its toxicological properties, as they have been often overlooked in search of protective factors. Stable dust samples from four Finnish dairy farms were collected by utilizing two different collection methods. Toxicological potential was analysed by stimulating co-cultures of lung epithelial and macrophage-like cells with dust. Size and mass distributions of airborne particles in the stables and bacterial and fungal microbiota of the dust were analysed. Stimulation with dust did not affect viability, but heightened oxidative stress responses and cytokine secretion, and slightly reduced the metabolic activity. There were a few differences in responses between farms, however, the differences were mainly in the intensity and not in the direction of the response. Cellular responses induced by dusts collected by different sampling methods did not differ substantially. Unprocessed stable dust samples showed relatively low direct toxicity but were able to trigger immune responses in studied cell model. This suggest that these dust collection methods could be utilized when investigating e.g. asthma-protective mechanisms.

Epidemiological evidence has shown the association between exposure to ambient fine particulate matter (PM) and increased susceptibility to bacterial and viral respiratory infections. However, to date, the underlying mechanisms of immunomodulatory effects of PM remain unclear. Our objective was to explore how exposure to relatively low doses of urban air PM alters innate responses to bacterial and viral stimuli in vitro. We used secondary alveolar epithelial cell line along with monocyte-derived macrophages to replicate innate lung barrier in vitro. Co-cultured cells were first exposed for 24 hours to PM2.5-1 (particle aerodynamic diameter between 1 and 2.5μm) and subsequently for an additional 24 hours to lipopolysaccharide (TLR4), polyinosinic-polycytidylic acid (TLR3), and synthetic single-stranded RNA oligoribonucleotides (TLR7/8) to mimic bacterial or viral stimulation. Toxicological endpoints included pro-inflammatory cytokines (IL-8, IL-6, and TNF-α), cellular metabolic activity, and cell cycle phase distribution. We show that cells exposed to PM2.5-1 produced higher levels of pro-inflammatory cytokines following stimulation with bacterial TLR4 ligand than cells exposed to PM2.5-1 or bacterial ligand alone. On the contrary, PM2.5-1 exposure reduced pro-inflammatory responses to viral ligands TLR3 and TLR7/8. Cell cycle analysis indicated that viral ligands induced cell cycle arrest at the G2-M phase. In PM-primed co-cultures, however, they failed to induce the G2-M phase arrest. Contrarily, bacterial stimulation caused a slight increase in cells in the sub-G1 phase but in PM2.5-1 primed co-cultures the effect of bacterial stimulation was masked by PM2.5-1. These findings indicate that PM2.5-1 may alter responses of immune defense differently against bacterial and viral infections. Further studies are required to explain the mechanism of immune modulation caused by PM in altering the susceptibility to respiratory infections., Highlights • Exposure to ambient PM increases susceptibility to respiratory infections. • Fine PM increased inflammatory response against bacterial stimulation in vitro. • Inflammatory response against viral stimulation was suppressed in PM treated cells. • Fine PM also altered the capacity of viral ligand to induce G2-M cell-cycle arrest.

The effect of cryopreservation on antigen-presenting cells (APCs) is understudied. It is important to understand the effects of cryopreservation on these cells as they play a major role in immune responses, and they could be utilized in different clinical applications. In this study, we compared fresh and cryopreserved PBMCs in regards of their general immune responsiveness and, furthermore, the effect of cryopreservation on the circulating APCs among PBMCs. We stimulated fresh and cryopreserved PBMCs (N = 6) with LPS or Poly(I:C).Cytokine production of PBMCs and expression of functional markers CD80 and ILT4 on major types of APCs, dendritic cells (DCs) and monocytes, were analysed. We also analysed whether cryopreservation affects different subtypes of DCs (plasmacytoid and myeloid DCs) differently. Cryopreserved PBMCs produced less cytokines than fresh cells in response to stimulation, but the response profiles were comparable. Cryopreservation had also an effect on the relative proportions of APCs. Stimuli-induced responses were somewhat parallel but weaker than those observed in fresh cells. This study suggests that the use of cryopreserved cells is more suitable in studies that assess general responses to stimuli instead of measuring exact levels of reactions. Thus, the interpretation and comparison of the results of different studies should not be done without considering the differences in cryopreservation techniques and their effects on PBMCs and, more specifically, on APCs.

Thermal isoeffect dose (TID) is a widely applied concept to evaluate the safety of medical devices that can expose patients to heat. However, it has rarely been used in photothermal therapy (PTT), where nanoparticles are used as light absorbers. Utilizing TID in an appropriate way would make it feasible to compare the results obtained with different light absorbers as well as clarifying their cellular effects. Herein, we apply TID as a definitive parameter to evaluate the outcomes of a nanoparticle-induced PTT in vitro. We show that cell death measured with an ATP-based viability assay and flow cytometry can be correlated with TID if time-temperature data is available. As an experimental model, black porous silicon nanoparticles were studied as photothermal agents to kill HeLa cancer cells. The results indicate that as the critical TID of 70 min is reached, the cells start to undergo apoptosis independently of the way in which the TID was attained: by long heating at low temperatures or by short heating at high temperatures. Overall, TID is proposed as a valid parameter which could be determined in the PTT studies to allow a straightforward comparison of the published results and the elucidation of the cell death mechanisms.

Background Early life farm exposures have been shown to decrease the risk of allergic diseases. Dendritic cells (DCs) may mediate asthma-protective effect of farm exposures as they play an important role in the development of immunity and tolerance. Our aim was to investigate whether the numbers and phenotypes of circulating DCs at age 6 are associated with farming, asthma, and atopy in a selected sample of French and Finnish children from the PASTURE study. Methods We studied 82 farm and 86 nonfarm children with and without asthma. Using flow cytometry, BDCA1+ CD11c+ myeloid DC1s (mDC1), BDCA3+high mDC2s and BDCA2+ plasmacytoid DCs (pDCs) were identified and expressions of CD86, immunoglobulin-like transcript 3 (ILT3) and ILT4 were analyzed. Questionnaires were used to assess prenatal and lifetime patterns of farm exposures and to define asthma. Atopic sensitization was defined by specific IgE measurements. Results The percentage of mDC2 cells was lower in farm children (0.033 ± 0.001) than in nonfarm children (0.042 ± 0.001; P = 0.008). Similar associations were found between mDC2 percentage and prenatal (P = 0.02) and lifetime exposure to farm milk (P = 0.03) and stables (P = 0.003), but these associations were not independent from farming. Asthma was positively associated with ILT4 + mDCs (P = 0.04) and negatively with CD86 + pDCs (P = 0.048) but only in nonfarm children. Conclusions Inverse association between farm exposure and mDC2 percentage suggest that this DC subset may play a role in farm-related immunoregulation.

PROBLEM Birth-related factors and neonatal treatments could affect the maturation of immune system and thus have lasting effects on immune responses. We investigated the effect of obstetric factors other than being born by cesarean section on immune responses later in life. METHOD OF STUDY Regulatory, inflammatory, TH1 and TH2 cytokines, and a chemokine were analyzed in unstimulated and Toll-like receptors (TLRs) 2-, 3-, and 4-stimulated PBMCs of teenagers born by cesarean delivery (CD; N=79). Data on obstetric factors were collected from patient data archives. RESULTS Advanced cervical dilatation at the time of CD associated with higher unstimulated production of cytokines compared to adolescents who were delivered before the onset of labor. Neonatal intensive care treatment associated with lower unstimulated production of cytokines. Similar associations were found following TLR stimulations. CONCLUSION The lack of natural processes of delivery and neonatal intensive care treatment might lead to long-lasting impairment of immune responses.

Additional file 6 Table S2. All measured organic compounds from wood combustion emissions. Organic compounds were sampled over 4-h exposure. Concentrations are calculated as averages from three test cycles ± standard deviation.

Additional file 1: Table S1. Calibration and quantification mixtures of isotope labelled internal standards and calibration standards.

Additional file 6 Table S2. All measured organic compounds from wood combustion emissions. Organic compounds were sampled over 4-h exposure. Concentrations are calculated as averages from three test cycles ± standard deviation.

Additional file 3 Figure S1. Physical properties in the diluted exposure exhaust per day to day, for spruce (A) and pine (B) experiments. Parts A and C show average of 3 experiment days total suspended particulate mass (TSP), lung deposited surface area (LDSA) and particle number concentration (PNC) during exposures.

Additional file 1: Table S1. Calibration and quantification mixtures of isotope labelled internal standards and calibration standards.

Additional file 3 Figure S1. Physical properties in the diluted exposure exhaust per day to day, for spruce (A) and pine (B) experiments. Parts A and C show average of 3 experiment days total suspended particulate mass (TSP), lung deposited surface area (LDSA) and particle number concentration (PNC) during exposures.