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12 result(s) for "Ruscitti, Cecilia"
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Locally instructed CXCR4hi neutrophils trigger environment-driven allergic asthma through the release of neutrophil extracellular traps
Low exposure to microbial products, respiratory viral infections and air pollution are major risk factors for allergic asthma, yet the mechanistic links between such conditions and host susceptibility to type 2 allergic disorders remain unclear. Through the use of single-cell RNA sequencing, we characterized lung neutrophils in mice exposed to a pro-allergic low dose of lipopolysaccharide (LPS) or a protective high dose of LPS before exposure to house dust mites. Unlike exposure to a high dose of LPS, exposure to a low dose of LPS instructed recruited neutrophils to upregulate their expression of the chemokine receptor CXCR4 and to release neutrophil extracellular traps. Low-dose LPS–induced neutrophils and neutrophil extracellular traps potentiated the uptake of house dust mites by CD11b + Ly-6C + dendritic cells and type 2 allergic airway inflammation in response to house dust mites. Neutrophil extracellular traps derived from CXCR4 hi neutrophils were also needed to mediate allergic asthma triggered by infection with influenza virus or exposure to ozone. Our study indicates that apparently unrelated environmental risk factors can shape recruited lung neutrophils to promote the initiation of allergic asthma. Marichal and colleagues show that lung neutrophils in mice exposed to three distinct pro-allergic conditions release neutrophil extracellular traps that potentiate allergen uptake by dendritic cells and type 2 allergic inflammation.
Non-classical tissue monocytes and two functionally distinct populations of interstitial macrophages populate the mouse lung
Resident tissue macrophages (RTM) can fulfill various tasks during development, homeostasis, inflammation and repair. In the lung, non-alveolar RTM, called interstitial macrophages (IM), importantly contribute to tissue homeostasis but remain little characterized. Here we show, using single-cell RNA-sequencing (scRNA-seq), two phenotypically distinct subpopulations of long-lived monocyte-derived IM, i.e. CD206 + and CD206 − IM, as well as a discrete population of extravasating CD64 + CD16.2 + monocytes. CD206 + IM are peribronchial self-maintaining RTM that constitutively produce high levels of chemokines and immunosuppressive cytokines. Conversely, CD206 − IM preferentially populate the alveolar interstitium and exhibit features of antigen-presenting cells. In addition, our data support that CD64 + CD16.2 + monocytes arise from intravascular Ly-6C lo patrolling monocytes that enter the tissue at steady-state to become putative precursors of CD206 − IM. This study expands our knowledge about the complexity of lung IM and reveals an ontogenic pathway for one IM subset, an important step for elaborating future macrophage-targeted therapies. Functional diversity of tissue-resident macrophages and signals governing their ontogeny and turnover remain unknown for the majority of tissues. Here the authors describe two phenotypically and functionally distinct long-lived populations of lung interstitial macrophages and their putative blood-derived monocytic precursor.
MafB-restricted local monocyte proliferation precedes lung interstitial macrophage differentiation
Resident tissue macrophages (RTMs) are differentiated immune cells that populate distinct niches and exert important tissue-supportive functions. RTM maintenance is thought to rely either on differentiation from monocytes or on RTM self-renewal. Here, we used a mouse model of inducible lung interstitial macrophage (IM) niche depletion and refilling to investigate the development of IMs in vivo. Using time-course single-cell RNA-sequencing analyses, bone marrow chimeras and gene targeting, we found that engrafted Ly6C + classical monocytes proliferated locally in a Csf1 receptor-dependent manner before differentiating into IMs. The transition from monocyte proliferation toward IM subset specification was controlled by the transcription factor MafB, while c-Maf specifically regulated the identity of the CD206 + IM subset. Our data provide evidence that, in the mononuclear phagocyte system, the ability to proliferate is not merely restricted to myeloid progenitor cells and mature RTMs but is also a tightly regulated capability of monocytes developing into RTMs in vivo. Marichal and colleagues use a model of niche depletion and refilling to show that engrafted Ly6C + classical monocytes proliferate locally in a Csf1 receptor-dependent manner before differentiating into lung interstitial macrophages.
Locally instructed CXCR4(hi) neutrophils trigger environment-driven allergic asthma through the release of neutrophil extracellular traps
Low exposure to microbial products, respiratory viral infections and air pollution are major risk factors for allergic asthma, yet the mechanistic links between such conditions and host susceptibility to type 2 allergic disorders remain unclear. Through the use of single-cell RNA sequencing, we characterized lung neutrophils in mice exposed to a pro-allergic low dose of lipopolysaccharide (LPS) or a protective high dose of LPS before exposure to house dust mites. Unlike exposure to a high dose of LPS, exposure to a low dose of LPS instructed recruited neutrophils to upregulate their expression of the chemokine receptor CXCR4 and to release neutrophil extracellular traps. Low-dose LPS-induced neutrophils and neutrophil extracellular traps potentiated the uptake of house dust mites by CD11b(+)Ly-6C(+) dendritic cells and type 2 allergic airway inflammation in response to house dust mites. Neutrophil extracellular traps derived from CXCR4(hi) neutrophils were also needed to mediate allergic asthma triggered by infection with influenza virus or exposure to ozone. Our study indicates that apparently unrelated environmental risk factors can shape recruited lung neutrophils to promote the initiation of allergic asthma.
Locally instructed CXCR4.sup.hi neutrophils trigger environment-driven allergic asthma through the release of neutrophil extracellular traps
Low exposure to microbial products, respiratory viral infections and air pollution are major risk factors for allergic asthma, yet the mechanistic links between such conditions and host susceptibility to type 2 allergic disorders remain unclear. Through the use of single-cell RNA sequencing, we characterized lung neutrophils in mice exposed to a pro-allergic low dose of lipopolysaccharide (LPS) or a protective high dose of LPS before exposure to house dust mites. Unlike exposure to a high dose of LPS, exposure to a low dose of LPS instructed recruited neutrophils to upregulate their expression of the chemokine receptor CXCR4 and to release neutrophil extracellular traps. Low-dose LPS-induced neutrophils and neutrophil extracellular traps potentiated the uptake of house dust mites by CD11b.sup.+Ly-6C.sup.+ dendritic cells and type 2 allergic airway inflammation in response to house dust mites. Neutrophil extracellular traps derived from CXCR4.sup.hi neutrophils were also needed to mediate allergic asthma triggered by infection with influenza virus or exposure to ozone. Our study indicates that apparently unrelated environmental risk factors can shape recruited lung neutrophils to promote the initiation of allergic asthma.
Spatiotemporal and Functional Investigation of Atypical Ly6G+ Macrophages Recruited After Lung Injury
En raison de leur structure et de leur rôle dans la respiration, les poumons sont continuellement exposés aux agents pathogènes présents dans l'air. Parmi ceux-ci, les virus respiratoires causent une mortalité importante et représentent un fardeau économique considérable. Les virus respiratoires courants entraînent généralement des infections légères et de courte durée, mais la pandémie de COVID-19 a révélé un taux élevé de persistance des pathologies respiratoires après des infections aiguës. Ces séquelles chroniques résultent de l'échec des mécanismes efficaces de réparation pulmonaire, entraînant fibrose, remodelage tissulaire anormal et bronchiolisation alvéolaire. Les cellules myéloïdes jouent un rôle central dans la réponse immunitaire lors des infections respiratoires et leurs fonctions pendant l'infection active sont bien caractérisées. Cependant, leurs fonctions pendant la phase de récupération restent peu comprises. Afin d’étudier les réponses immunitaires au cours de la réparation pulmonaire, un modèle murin cliniquement pertinent d’infection par le virus de la grippe A (utilisant la souche H1N1 PR8) a été employé. Des technologies de pointe, incluant le séquençage d'ARN unicellulaire, la transcriptomique spatiale, les tests métaboliques, la cytométrie en flux multiplexe et la microscopie, combinées à des modèles de chimères de moelle osseuse et des souris transgéniques, ont permis une analyse approfondie des populations de cellules myéloïdes durant les premières phases de réparation pulmonaire. Cette approche exhaustive a conduit à l'identification et à la caractérisation d'une population de macrophages dérivés de monocytes encore inconnue présente dans les poumons lors de la phase de récupération précoce. Ces macrophages, à courte durée de vie et exprimant Ly6G, sont recrutés après le pic de l'infection dans les alvéoles périlésionnelles en régénération, où ils montrent de fortes capacités d’efferocytose et sécrètent des molécules facilitant la résolution de l'inflammation. De plus, les macrophages Ly6G+ jouent un rôle crucial dans la promotion de la régénération alvéolaire en interagissant avec les cellules épithéliales alvéolaires de type 2, progénitrices de l'épithélium alvéolaire et en soutenant leur rôle essentiel dans la réparation alvéolaire fonctionnelle. La présence de ce phénotype de macrophages a été observée dans d'autres modèles, incluant les lésions pulmonaires induites par la bléomycine et les dommages hépatiques aigus induits par le paracétamol, indiquant un rôle conservé à travers différents types et sites de lésions. Enfin, la pertinence potentielle de ces découvertes a été explorée en analysant les cellules de lavage bronchoalvéolaire chez des patients atteints de pneumonie, où des cellules semblables aux macrophages Ly6G+ ont été identifiées. Nos résultats enrichissent la compréhension des mécanismes myéloïdes impliqués dans la régénération alvéolaire et suggèrent que la manipulation de ces macrophages pourrait constituer une stratégie pour améliorer la réparation pulmonaire après une lésion pulmonaire infectieuse aiguë.
Locally instructed CXCR4 hi neutrophils trigger environment-driven allergic asthma through the release of neutrophil extracellular traps
Low exposure to microbial products, respiratory viral infections and air pollution are major risk factors for allergic asthma, yet the mechanistic links between such conditions and host susceptibility to type 2 allergic disorders remain unclear. Through the use of single-cell RNA sequencing, we characterized lung neutrophils in mice exposed to a pro-allergic low dose of lipopolysaccharide (LPS) or a protective high dose of LPS before exposure to house dust mites. Unlike exposure to a high dose of LPS, exposure to a low dose of LPS instructed recruited neutrophils to upregulate their expression of the chemokine receptor CXCR4 and to release neutrophil extracellular traps. Low-dose LPS-induced neutrophils and neutrophil extracellular traps potentiated the uptake of house dust mites by CD11b Ly-6C dendritic cells and type 2 allergic airway inflammation in response to house dust mites. Neutrophil extracellular traps derived from CXCR4 neutrophils were also needed to mediate allergic asthma triggered by infection with influenza virus or exposure to ozone. Our study indicates that apparently unrelated environmental risk factors can shape recruited lung neutrophils to promote the initiation of allergic asthma.
The potential of melatonin in the mitigation of adverse effects of salt stress in basil (Ocimum basilicum L.) plants
Background Drought and salinity are among the most critical abiotic stresses affecting crops worldwide. Within this context, melatonin has emerged as a multifunctional signaling molecule that mitigates stress and promotes growth in various plant species. This study aimed to evaluate the physiological and biochemical responses of Ocimum basilicum plants cultivated under hydroponic conditions and exposed to salt stress, following pre-harvest treatment with melatonin. Basil seedlings were immersed in melatonin solutions at concentrations ranging from 0 to 100 μM for 48 hours and subsequently grown for 60 days under saline stress. Results Melatonin treatment, particularly at 50 μM (T50), significantly increased the fresh weight of both aerial parts and roots. Aerial biomass nearly doubled, reaching 47.6 g plant⁻¹ compared to 23.8 g plant⁻¹ in untreated plants under salinity (+100%). Root fresh weight also rose markedly, from 29.6 g plant⁻¹ to 50.3 g plant⁻¹ (+69.8%). Leaf area expanded substantially, averaging 660.8 cm² per plant at T50 versus 301.2 cm² in salinity-stressed controls (+119.4%). Total chlorophyll content increased by 3.9–11.2%, with values rising from 43.43 µg cm⁻² in untreated plants under salinity to a maximum of 48.29 µg cm⁻² at 25 μM melatonin. Stomatal conductance showed a significant improvement as well, reaching 169.4 mmol m⁻² s⁻¹ at T50, which represented a 50.6% increase relative to untreated plants. Biochemical stress indicators declined consistently in melatonin-treated plants. MDA content decreased by 36.2% (from 3.87 to 2.47 nmol mg⁻¹ FW at T50), while foliar proline accumulation was reduced by 28.1% under the same treatment. Leaf total phenol content followed a similar trend, showing reductions ranging from 19.2 to 48.1% across all melatonin doses compared with salt-stressed controls. In most cases, these decreases were statistically significant (P<0.05), indicating improved redox homeostasis and membrane stability under salt stress. Conclusions Among the tested concentrations, 50 μM melatonin was the most effective in promoting growth and alleviating stress. These findings highlight its potential as a pre-harvest strategy to enhance basil performance under salinity within the broader context of melatonin-based stress management.
D-Leu1MC-LR and MC-LR: A Small–Large Difference: Significantly Different Effects on Phaseolus vulgaris L. (Fabaceae) Growth and Phototropic Response after Single Contact During Imbibition with Each of These Microcystin Variants
[D-Leu1]MC-LR and MC-LR, two microcystins differing in one amino acid, constitute a sanitary and environmental problem owing to their frequent and concomitant presence in water bodies of the Americas and their association with human intoxication during recreational exposure to cyanobacterial bloom. Present in reservoirs used for irrigation as well, they can generate problems in the development of crops such as Phaseolus vulgaris, of nutritional and economic interest to the region. Although numerous works address the toxic effects of MC-LR, information on the toxicity of [D-Leu1]MC-LR is limited. Our objective was to study the toxic effects of [D-Leu1]MC-LR and MC-LR (3.5 µg/ml) on P. vulgaris after a single contact at the imbibition stage. Our findings indicate that 10 days post treatment, [D-Leu1]MC-LR generates morphological and physiological alterations more pronounced than those caused by MC-LR. In addition to the alterations produced by [D-Leu1]MC-LR in the development of seedlings and the structure of the leaves, roots and stems, we also found alterations in leaf stomatal density and conductivity, a longer delay in the phototropic response and a decrease in the maximum curvature angles achieved with respect to that observed for MC-LR. Our findings indicate that these alterations are linked to the greater inhibition of phosphatase activity generated by [D-Leu1]MC-LR, rather than to oxidative damage. We observed that 30 days after treatment with MC-LR, plants presented better development and recovery than those treated with [D-Leu1]MC-LR. Further studies are required on [D-Leu1]MC-LR and MC-LR toxicity and their underlying mechanisms of action.
Evaluation of two nematophagous fungi for the control of false root-knot nematode Nacobbus aberrans in pepper crops
Nacobbus aberrans is an endophytic parasitic nematode that induces root galls, negatively affecting plant growth and development, and decreasing the production of economically important crops . Currently, low environmental impact alternatives are being developed for the control of nematodes, such as biological control agents, to reduce the use of soil disinfectants. Nematophagous fungi are microorganisms that can suppress nematode reproduction due to different mechanisms, such as parasitism of eggs, toxin production and stimulation of plant growth. The aim of this study was to investigate the effect of inoculation with nematophagous fungi on N. aberrans in greenhouse-grown pepper ( Capsicum anuumm L.) plants and to analyze the response of the infected plants. Two fungal isolates, Purpureocillium lilacimum and Pleurotus ostreatus were tested. The plants were inoculated with these fungi at the time of transplantation in the presence and absence of N. aberrans. The reproduction factor of the nematode was 23.17; 5.90 and 36.4 for P. lilacinum, P. ostreatus and control, respectively. Both in plants parasitized and not parasitized by nematodes, the fungi increased the content of soluble proteins and photosynthetic pigments. Additionally, a favorable impact on growth parameters was also observed. This beneficial effect was also verified by a lower accumulation of proline and sugars, metabolites used by plants as osmoregulators in stress situations, and a low accumulation of malondialdehyde, a metabolite resulting from oxidative stress. These results show that both fungi are suitable for use in the biocontrol of N. aberrans and as growth promoters in plants.