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BACKGROUND: Asthma is often accompanied by type 2 immunity rich in IL-4, IL-5 and IL-13 cytokines produced by TH2 lymphocytes or type 2 innate lymphoid cells (ILC2s). Interleukin-2 family cytokines play a key role in the differentiation, homeostasis and effector function of innate and adaptive lymphocytes. OBJECTIVE: IL-9 and IL-21 boost the activation and proliferation of TH2 and ILC2s, but the relative importance and potential synergism between these γc cytokines is currently unknown. METHODS: Using newly generated antibodies, we inhibited IL-9 and IL-21 alone or in combination, in various murine models of asthma. In a translational approach using segmental allergen challenge, we recently described elevated IL-9 levels in human allergic asthmatics in comparison to non-asthmatic controls. Here, we also measured IL-21 in both groups. RESULTS: IL-9 played a central role in controlling innate IL-33 induced lung inflammation by promoting proliferation and activation of ILC2s, in an IL-21 independent manner. Conversely, chronic house dust mite induced airway inflammation, mainly driven by adaptive immunity, was solely dependent on IL-21, that controlled TH2 activation, eosinophilia, total serum IgE and formation of tertiary lymphoid structures. In a model of innate on adaptive immunity driven by papain allergen, a clear synergy was found between both pathways, since combined anti-IL-9 or anti-IL-21 blockade was superior in reducing key asthma features. In human bronchoalveolar lavage (BAL) samples we measured elevated IL-21 protein within the allergic asthmatic group, compared with the allergic control group. We also found increased IL21R transcripts and predicted IL-21 ligand activity in various disease-associated cell subsets. CONCLUSION: IL-9 and IL-21 play important and non-redundant roles in allergic asthma by boosting ILC2s and TH2 cells, revealing a dual IL-9 and IL-21 targeting strategy as a new and testable approach.
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A large body of evidence is documenting the impact of reduced pH on marine species and ecosystems. This information is used to infer the present and future impacts of ocean acidification. However, a vast majority of the studies were performed using constant pH and the high level of pH variability experienced by marine organisms on the coastal zone was often overlooked. Recent studies highlight the key role of this variability in driving biological response to pH as well as species sensitivity to ocean acidification. For example, it was hypothesized that because of local adaptation, the extreme of the present range of pH variability is a good predictor for local biological thresholds. Using a complex experimental design, we investigated what part of the pH variability is driving the biological response of the sea urchin Echinus esculentus larvae. Comparing stable (pH 8.13, 7.82, 7.53) and fluctuating treatments (12 h at pH 8.13 and 12 h at pH 7.53) following natural or inverted diurnal cycles, we were able to show that (i) under constant conditions, low pH deviating from the present range of natural variability had a negative effect on larval growth rate and calcification; (ii) under fluctuating conditions, a desynchronization of the pH variation with the photoperiod led to decreased larval growth rate and calcification; (iii) overall, larval fitness (survival, growth and calcification) was higher under fluctuating conditions as compared to constant. While these data do not support the hypothesis that the minimum pH is the main driver of the biological response, they provide evidence of adaptation to variability in a coastal species with associated a cost of plasticity but not a cost of canalization.
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Larva , Ouriços-do-Mar , Água do Mar , Animais , Concentração de Íons de Hidrogênio , Larva/crescimento & desenvolvimento , Larva/fisiologia , Água do Mar/química , Ouriços-do-Mar/fisiologia , Ecossistema , Adaptação FisiológicaRESUMO
Bioluminescence is the production of visible light by living organisms thanks to a chemical reaction, implying the oxidation of a substrate called luciferin catalyzed by an enzyme, the luciferase. The luminous brittle star Amphiura filiformis depends on coelenterazine (i.e., the most widespread luciferin in marine ecosystems) and a luciferase homologous to the cnidarian Renilla luciferase to produce blue flashes in the arm's spine. Only a few studies have focused on the ontogenic apparitions of bioluminescence in marine organisms. Like most ophiuroids, A. filiformis displays planktonic ophiopluteus larvae for which the ability to produce light was not investigated. This study aims to document the apparition of the luminous capabilities of this species during its ontogenic development, from the egg to settlement. Through biochemical assays, pharmacological stimulation, and Renilla-like luciferase immunohistological detection across different developing stages, we pointed out the emergence of the luminous capabilities after the ophiopluteus larval metamorphosis into a juvenile. In conclusion, we demonstrated that the larval pelagic stage of A. filiformis is not bioluminescent compared to juveniles and adults.
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Equinodermos , Ecossistema , Animais , Organismos Aquáticos , Luciferases/química , Larva , LuciferinasRESUMO
Micro-/nano-plastic particles (MNPs) are present in the ocean with potential detrimental impacts on marine ecosystems. Bivalves are often used as marine bioindicators and are ideal to evaluate the threat posed by various-sized MNPs. We exposed the mussel Mytilus coruscus to MNPs with different particle sizes (70 and 500 nm, 5, 10 and 100 µm) for 3, 72 h and 30 days. The antioxidant responses in digestive gland and the hemolymph were then evaluated. The time of exposure played a strong modulating role in the biological response. A 3-hour exposure had no significant impact on the digestive gland. After 72 h, an increase in oxidative stress was observed in the digestive gland, including increased hydrogen peroxide (H2O2) level, catalase (CAT), glutathione peroxidase (GPx) activities and malondialdehyde (MDA) production. After a 30-day exposure, the oxidative stress decreased while lipid peroxidation increased. A 30-day exposure increased hemocyte mortality (HM) and reactive oxygen species (ROS) levels in the hemolymph, while phagocytosis (PA), lysosome content (LC), mitochondrial number (MN) and mitochondrial membrane potential (MMP) significantly decreased. Longer-term exposure to MNPs caused oxidative stress in the digestive gland as well as impaired viability and immunity of hemocytes. Particle size also influenced the response with smaller particles having more severe effects. A depuration for 7 days was enough to reverse the negative effects observed on the digestive gland and hemolymph. This study provides new insights on the effects of small-sized MNPs, especially nanoplastic particles (NPs), on aquatic organisms, and provides a solid theoretical knowledge background for future studies on toxic effects of MNPs.
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Mytilus , Poluentes Químicos da Água , Animais , Antioxidantes/farmacologia , Mytilus/fisiologia , Ecossistema , Peróxido de Hidrogênio/farmacologia , Imunidade , Poluentes Químicos da Água/toxicidadeRESUMO
Coastal ecosystems experience large environmental variability leading to local adaptation. The key role of variability and adaptation in modulating the biological sensitivity to ocean acidification is increasingly acknowledged. Monitoring and understanding the ecological niche at the right spatio-temporal scale is key to understand the sensitivity of any organism and ecosystems. However, the role of the variability in relevant carbonate chemistry parameters as a driver is often overlooked. For example, the balance between photosynthesis and respiration over the day/night cycle is leading to high pH/pCO2 variability in seagrass beds. We hypothesized that (i) the calcifying larvae of the sea urchin Echinus esculentus exposed to seagrass-driven variability would have some physiological mechanisms to respond to such variability; and (ii) these mechanisms would reach their limit under ocean acidification. We compared the presence and absence of the seagrass Zostera marina in flow through mesocosms fed with seawater with 4 pHs. The carbonate chemistry was monitored and biological response of a sea urchin larvae was documented over 3 weeks. Growth and net calcification rates were measured twice a day to encompass diurnal variability. Our results show that larvae growth rate significantly decreased with decreasing average pHT in both absence and presence of seagrass. Moreover, sea urchin larvae showed a slower growth rate in presence of seagrass, only visible in the lowest pH conditions. In addition, larvae raised in presence of seagrass, maximized calcification during the day, and lower their calcification during the night. In contrast, no significant difference was observed between day and night for the net calcification rate in larvae raised in absence of seagrass. Our results demonstrate the limit of local adaptation to the present range of variability under ocean acidification conditions. It also demonstrates that photosynthetic ecosystems such as seagrass may not play a role of refuge against future ocean acidification.
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Ecossistema , Água do Mar , Água do Mar/química , Concentração de Íons de Hidrogênio , Acidificação dos Oceanos , Carbonatos , Dióxido de Carbono/análise , Oceanos e MaresRESUMO
Bioluminescence, the ability of living organisms to emit visible light, is an important ecological feature for many marine species. To fulfil the ecological role (defence, offence, or communication), bioluminescence needs to be finely controlled. While many benthic anthozoans are luminous, the physiological control of light emission has only been investigated in the sea pansy, Renilla koellikeri. Through pharmacological investigations, a nervous catecholaminergic bioluminescence control was demonstrated for the common sea pen, Pennatula phosphorea, and the tall sea pen, Funiculina quadrangularis. Results highlight the involvement of adrenaline as the main neuroeffector triggering clusters of luminescent flashes. While noradrenaline and octopamine elicit flashes in P. phosphorea, these two biogenic amines do not trigger significant light production in F. quadrangularis. All these neurotransmitters act on both the endodermal photocytes located at the base and crown of autozooids and specific chambers of water-pumping siphonozooids. Combined with previous data on R. koellikeri, our results suggest that a catecholaminergic control mechanisms of bioluminescence may be conserved in Anthozoans.
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Anthropologic activities caused frequent eutrophication in coastal and estuarine waters, resulting in diel-cycling hypoxia. Given global climate change, extreme weather events often occur, thus salinity fluctuation frequently breaks out in these waters. This study aimed to evaluate the combined effects of salinity and hypoxia on intestinal microbiota and digestive enzymes of Crassostrea hongkongensis. Specifically, we sequenced 16 S rRNA of intestinal microbiota and measured the digestive enzymes trypsin (TRS), lipase (LPS) and amylase (AMY) in oysters exposed for 28 days to three salinities (10, 25 and 35) and two dissolved oxygen conditions, normoxia (6 mg/L) and hypoxia (6 mg/L for 12 h, 2 mg/L for 12 h). Oysters in normoxia and salinity of 25 were treated as control. After 28-day exposure, for microbial components, Fusobacteriota, Firmicutes, Bacteroidota, Proteobacteria and Actinobacteriota comprised the majority for all experimental groups. Compared with the control group, the diversity and structure of intestinal microbiota tended to change in all treated groups. The species richness in C. hongkongensis intestine also changed. It was the most significant that high salinity increased Proteobacteria proportion while low salinity and hypoxia increased Fusobacteriota but decreased Proteobacteria, respectively. Additionally, Actinobacteriota was sensitive and changed under environmental stressor (P < 0.01). The prediction results on intestinal microbiota showed that, all functions of oysters were up-regulated to distinct degrees under low/high salinity with hypoxia. According to the KEGG prediction, cellular processes were more active and energy metabolism upregulated, indicating the adaptation of C. hongkongensis to environmental change. Periodical hypoxia and low/high salinity had complex effect on the digestive enzymes, in which the activity of TRS and LPS decreased while AMY increased. High/low salinity and periodical hypoxia can change the secretion of digestive enzymes and influence intestinal microbial diversity and species richness of C. hongkongensis, deducing the chronic adverse effects on the digestive physiology in long-term exposure.
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Crassostrea , Microbioma Gastrointestinal , Animais , Crassostrea/metabolismo , Salinidade , Lipopolissacarídeos , HipóxiaRESUMO
Ocean acidification (OA) may either increase or have a neutral effect on the calcification in shrimp's exoskeleton. However, investigations on changes in the carbon composition of shrimp's exoskeletons under OA are lacking. We exposed juvenile Pacific white shrimps to target pHs of 8.0, 7.9, and 7.6 for 100 days to evaluate changes in carapace thickness, total carbon (TC), particulate organic carbon (POC), particulate inorganic carbon (PIC), calcium, and magnesium concentrations in their exoskeletons. The PIC: POC ratio of shrimp in pH 7.6 treatment was significantly higher by 175 % as compared to pH 8.0 treatment. Thickness and Ca% in pH 7.6 treatment were significantly higher as compared to pH 8.0 treatment (90 % and 65 %, respectively). This is the first direct evidence of an increased PIC: POC ratio in shrimp exoskeletons under OA. In the future, such changes in carbon composition may affect the shrimp population, ecosystem functions, and regional carbon cycle.
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Exoesqueleto Energizado , Água do Mar , Animais , Água do Mar/química , Carbono , Ecossistema , Concentração de Íons de Hidrogênio , Acidificação dos Oceanos , Dióxido de Carbono/química , Minerais , CrustáceosRESUMO
The Centre for Marine Evolutionary Biology (CeMEB) at the University of Gothenburg, Sweden, was established in 2008 through a 10-year research grant of 8.7 m to a team of senior researchers. Today, CeMEB members have contributed >500 scientific publications, 30 PhD theses and have organised 75 meetings and courses, including 18 three-day meetings and four conferences. What are the footprints of CeMEB, and how will the centre continue to play a national and international role as an important node of marine evolutionary research? In this perspective article, we first look back over the 10 years of CeMEB activities and briefly survey some of the many achievements of CeMEB. We furthermore compare the initial goals, as formulated in the grant application, with what has been achieved, and discuss challenges and milestones along the way. Finally, we bring forward some general lessons that can be learnt from a research funding of this type, and we also look ahead, discussing how CeMEB's achievements and lessons can be used as a springboard to the future of marine evolutionary biology.
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The prevalence and frequency of hypoxia events have increased worldwide over the past decade as a consequence of global climate change and coastal biological oxygen depletions. On the other hand, anthropogenic emissions of CO2 and consequent accumulation in the sea surface result in a perturbation of the seawater carbonate system, including a decrease in pH, known as ocean acidification. While the effect of decreases in pH and dissolved oxygen (DO) concentration is better understood, their combined effects are still poorly resolved. Here, we exposed adult mussels (Mytilus galloprovincialis) to two pHs (8.27 and 7.63) and DO concentrations (7.65 and 2.75 mg L-1) over 17 days in a full-factorial design. These levels correspond to extremes of the present natural variability and are relevant in the context of ocean acidification and hypoxia. No mortality was observed during the experiment. However, sublethal effects were observed for clearance and oxygen consumption rates, as well as total haemocytes count and haemocytes viability and gene expression in mussels exposed to the combination of low pH and low DO. Respiration and excretion rates were not significantly impacted by low pH and DO, alone or in combination. Overall, low pH alone led to a decrease in all tested physiological parameters while low DO alone led to a decline in clearance rate, haemocyte parameters and an increase in carbohydrate content. Both parameters led to up- or down-regulation of most of the selected genes. Not surprisingly, the combined effect of low pH and low DO could not be predicted by a simple arithmetic additive response at the effect level, highlighting more complex and non-linear effects.
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Mytilus , Animais , Oxigênio , Concentração de Íons de Hidrogênio , Água do Mar/química , Hipóxia , Expressão GênicaRESUMO
GM-CSF promotes myelopoiesis and inflammation, and GM-CSF blockade is being evaluated as a treatment for COVID-19-associated hyperinflammation. Alveolar GM-CSF is, however, required for monocytes to differentiate into alveolar macrophages (AMs) that control alveolar homeostasis. By mapping cross-species AM development to clinical lung samples, we discovered that COVID-19 is marked by defective GM-CSF-dependent AM instruction and accumulation of pro-inflammatory macrophages. In a multi-center, open-label RCT in 81 non-ventilated COVID-19 patients with respiratory failure, we found that inhalation of rhu-GM-CSF did not improve mean oxygenation parameters compared with standard treatment. However, more patients on GM-CSF had a clinical response, and GM-CSF inhalation induced higher numbers of virus-specific CD8 effector lymphocytes and class-switched B cells, without exacerbating systemic hyperinflammation. This translational proof-of-concept study provides a rationale for further testing of inhaled GM-CSF as a non-invasive treatment to improve alveolar gas exchange and simultaneously boost antiviral immunity in COVID-19. This study is registered at ClinicalTrials.gov (NCT04326920) and EudraCT (2020-001254-22).
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COVID-19 , Macrófagos Alveolares , Humanos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Pulmão , MacrófagosRESUMO
Using a targeted metabolomic approach we investigated the effects of low seawater pH on energy metabolism in two late copepodite stages (CIV and CV) of the keystone Arctic copepod species Calanus glacialis. Exposure to decreasing seawater pH (from 8.0 to 7.0) caused increased ATP, ADP and NAD+ and decreased AMP concentrations in stage CIV, and increased ATP and phospho-L-arginine and decreased AMP concentrations in stage CV. Metabolic pathway enrichment analysis showed enrichment of the TCA cycle and a range of amino acid metabolic pathways in both stages. Concentrations of lactate, malate, fumarate and alpha-ketoglutarate (all involved in the TCA cycle) increased in stage CIV, whereas only alpha-ketoglutarate increased in stage CV. Based on the pattern of concentration changes in glucose, pyruvate, TCA cycle metabolites, and free amino acids, we hypothesise that ocean acidification will lead to a shift in energy production from carbohydrate metabolism in the glycolysis toward amino acid metabolism in the TCA cycle and oxidative phosphorylation in stage CIV. In stage CV, concentrations of most of the analysed free fatty acids increased, suggesting in particular that ocean acidification increases the metabolism of stored wax esters in this stage. Moreover, aminoacyl-tRNA biosynthesis was enriched in both stages indicating increased enzyme production to handle low pH stress.
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Copépodes , Água do Mar , Animais , Acidificação dos Oceanos , Concentração de Íons de Hidrogênio , Ácidos Cetoglutáricos , Trifosfato de Adenosina , AminoácidosRESUMO
As global climate change has dramatically impacted the ocean, severe temperature elevation and a decline in primary productivity has frequently occurred, which has affected the structure of coastal biomes. In this study, the sex-specific responses to temperature change and food availability in mussels were determined in terms of digestive performance. The thick-shelled mussels Mytilus coruscus (male and female) were exposed to different temperature and nutritional conditions for 30 days. The results showed that the digestive enzymes of mussels were significantly affected by temperature, food, sex, and their interactions. High temperature (30°C) and starvation significantly decreased amylase, lysozyme, and pepsase activities of female mussels, while trypsin and trehalase did not change significantly at the experimental end. The activity of amylase, trypsin, and trehalase was significantly reduced in males at high temperature (30°C) under starvation treatment, but high temperature (30°C) elevated pepsase. Unsurprisingly, starvation caused the reduction of lysozyme and pepsase under 25°C in males. Amylase, lipase, and trehalase were higher in female mussels compared with males, while the enzymatic activities of lysozyme, pepsase, and trypsin were higher in male mussels than females. Principal component analysis showed that different enzyme activity indexes were separated in male and female mussels, indicating that male and female mussels exhibited significantly different digestive abilities under temperature and food condition change. The study clarified sex-specific response difference in mussel digestive enzymes under warming and starvation and provided guidance for the development of mussel aquaculture (high temperature management and feeding strategy) under changing marine environments.
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Molecular biology holds a vast potential for tackling climate change and biodiversity loss. Yet, it is largely absent from the current strategies. We call for a community-wide action to bring molecular biology to the forefront of climate change solutions.
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Biodiversidade , Mudança Climática , Ecossistema , Biologia MolecularRESUMO
Ongoing ocean acidification is expected to affect marine organisms and ecosystems. While sea urchins can tolerate a wide range of pH, this comes at a high energetic cost, and early life stages are particularly vulnerable. Information on how ocean acidification affects transitions between life-history stages is scarce. We evaluated the direct and indirect effects of pH (pHT 8.0, 7.6 and 7.2) on the development and transition between life-history stages of the sea urchin Strongylocentrotus droebachiensis, from fertilization to early juvenile. Continuous exposure to low pH negatively affected larval mortality and growth. At pH 7.2, formation of the rudiment (the primordial juvenile) was delayed by two days. Larvae raised at pH 8.0 and transferred to 7.2 after competency had mortality rates five to six times lower than those kept at 8.0, indicating that pH also has a direct effect on older, competent larvae. Latent effects were visible on the larvae raised at pH 7.6: they were more successful in settling (45% at day 40 post-fertilization) and metamorphosing (30%) than larvae raised at 8.0 (17 and 1% respectively). These direct and indirect effects of ocean acidification on settlement and metamorphosis have important implications for population survival.
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Plâncton , Strongylocentrotus , Animais , Ecossistema , Concentração de Íons de Hidrogênio , Larva , Oceanos e Mares , Água do Mar/químicaRESUMO
Anthropogenic CO2 emissions have led to the warming and acidification of the oceans. Although, there is a growing of evidence showing that simultaneous occurrence of ocean acidification and ocean warming are threats to marine organisms, information on their combined effect on coastal shrimp species remains scarce. The purpose of this study was to estimate the combined effects of seawater acidification and warming on growth-related traits and biochemical responses of P. elegans juveniles. In this work, shrimp were exposed for 65 days at 4 experimental conditions: pH 8.10 * 18 °C, pH 7.80 * 18 °C, pH 8.10 * 22 °C, pH 7.80 * 22 °C. The results showed that low pH decreases the lipid content by â¼13% (p < 0.05). Higher temperature reduced the condition factor by â¼11%, the protein content by â¼20%, the PUFA by â¼8,6% and shortened moulting events by 5 days (p > 0.05) while the SFA increased â¼9.4%. The decrease in condition factor and protein was however more prominent in organisms exposed to the combination of pH and temperature with a decrease of â¼13% and â¼21%, respectively. Furthermore, essential fatty acids as EPA and DHA also decreased by â¼20% and â¼6.6% in low pH and higher temperature condition. Despite this study suggest that warming may have a greater impact than acidification, it has been shown that their combined effect can exacerbate these impacts with consequences for the shrimp's body size and biochemical profile.
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Palaemonidae , Água do Mar , Animais , Aquecimento Global , Concentração de Íons de Hidrogênio , Oceanos e Mares , Água do Mar/química , TemperaturaRESUMO
Ocean acidification has emerged as a major concern in the last fifteen years and studies on the impacts of seawater acidification on marine organisms have multiplied accordingly. This review aimed at synthesizing the literature on the effects of seawater acidification on tropical scleractinians under laboratory-controlled conditions. We identified 141 articles (published between 1999 and 2021) and separated endpoints into 22 biological categories to identify global trends for mitigation and gaps in knowledge and research priorities for future investigators. The relative number of affected endpoints increased with pH intensity (particularly for endpoints associated to calcification and reproduction). When exposed to pH 7.6-7.8 (compared to higher pH), 49% of endpoints were affected. The diversity in experimental designs prevented deciphering the modulating role of coral life stages, genera or duration of exposure. Finally, important bias in research efforts included most experiments on adult corals (68.5%), in 27 out of 150 (18%) coral ecoregions and exclusively from shallow-waters.
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Antozoários , Animais , Antozoários/química , Calcificação Fisiológica , Recifes de Corais , Concentração de Íons de Hidrogênio , Água do Mar/químicaRESUMO
The omnipresence of microplastic (MP) in various environmental samples, including aerosols, has raised public health concerns; however, there is presently very limited information on MPs in indoor aerosol. This paper presents a unique dataset where smaller MPs have been sampled using a six-stage cascade impactor from indoor environments in Kuwait. The MP concentration in the indoor air varied between 3.2 and 27.1 particles m-3, and the relative MP concentration decreased linearly from the lowest to the highest size fraction. A significant effect of location was observed for the total number of MPs (F2,14 = 5.80, p = 0.02) and the inhalable fraction (F2,14 = 8.38, p = 0.005), while location had no effect on the respirable fraction (F2,14 = 0.54, p = 0.60). A significant effect of the type of air conditioning used was also observed for the total number of MPs (F2,19 = 5.58, p = 0.01) and the inhalable fraction (F2,19 = 6.45, p = 0.008), while location had no effect on the respirable fraction (F2,19 = 1.30, p = 0.30). For the total number of MPs and the inhalable fraction, the concentration was significantly higher for the split unit air-conditioning as compared to the central air-conditioning plants. The presence/absence of carpets had no significant effect on the MP concentrations (total: F1,19 = 4.08, p = 0.06; inhalable: F1,19 = 3.03, p = 0.10; respirable: F1,19 = 4.27, p = 0.05). The shape was dominantly fibers, with few fragments in lower size fractions. These datasets represent the first baseline information for Kuwait, and the smaller MPs in all the samples further underscore the need to develop standardized protocols of MP collection in the ≤2.5 µm fraction that can have more conspicuous health implications.
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In rare instances, pediatric SARS-CoV-2 infection results in a novel immunodysregulation syndrome termed multisystem inflammatory syndrome in children (MIS-C). We compared MIS-C immunopathology with severe COVID-19 in adults. MIS-C does not result in pneumocyte damage but is associated with vascular endotheliitis and gastrointestinal epithelial injury. In MIS-C, the cytokine release syndrome is characterized by IFNγ and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFNγ levels correlate with granzyme B production in CD16+ NK cells and TIM3 expression on CD38+/HLA-DR+ T cells. Single-cell TCR profiling reveals a skewed TCRß repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3+/CD38+/HLA-DR+ T cells. Using NicheNet, we confirm IFNγ as a central cytokine in the communication between TIM3+/CD38+/HLA-DR+ T cells, CD16+ NK cells, and patrolling monocytes. Normalization of IFNγ, loss of TIM3, quiescence of CD16+ NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis.