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Lung-resident (LR) mesenchymal stem and stromal cells (MSCs) are key elements of the alveolar niche and fundamental regulators of homeostasis and regeneration. We interrogated their function during virus-induced lung injury using the highly prevalent respiratory syncytial virus (RSV) which causes severe outcomes in infants. We applied complementary approaches with primary pediatric LR-MSCs and a state-of-the-art model of human RSV infection in lamb. Remarkably, RSV-infection of pediatric LR-MSCs led to a robust activation, characterized by a strong antiviral and pro-inflammatory phenotype combined with mediators related to T cell function. In line with this, following in vivo infection, RSV invades and activates LR-MSCs, resulting in the expansion of the pulmonary MSC pool. Moreover, the global transcriptional response of LR-MSCs appears to follow RSV disease, switching from an early antiviral signature to repair mechanisms including differentiation, tissue remodeling, and angiogenesis. These findings demonstrate the involvement of LR-MSCs during virus-mediated acute lung injury and may have therapeutic implications., Competing Interests: The authors have declared that no competing interests exist.

The human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, possibly due to the properties of the immature neonatal pulmonary immune system. Using the newborn lamb, a classical model of human lung development and a translational model of RSV infection, we aimed to explore the role of cell-mediated immunity in RSV disease during early life. Remarkably, in healthy conditions, the developing T cell compartment of the neonatal lung showed major differences to that seen in the mature adult lung. The most striking observation being a high baseline frequency of bronchoalveolar IL-4-producing CD4+ and CD8+ T cells, which declined progressively over developmental age. RSV infection exacerbated this pro-type 2 environment in the bronchoalveolar space, rather than inducing a type 2 response per se. Moreover, regulatory T cell suppressive functions occurred very early to dampen this pro-type 2 environment, rather than shutting them down afterwards, while γδ T cells dropped and failed to produce IL-17. Importantly, RSV disease severity was related to the magnitude of those unconventional bronchoalveolar T cell responses. These findings provide novel insights in the mechanisms of RSV immunopathogenesis in early life, and constitute a major step for the understanding of RSV disease severity., Competing Interests: The authors have declared that no competing interests exist.

With substantial progress of nanotechnology, there is rising concern about possible adverse health effects related to inhalation of nanomaterials, such as multi-walled carbon nanotubes (MWCNT). In particular, individuals with chronic respiratory disorders, such as chronic obstructive pulmonary disease (COPD), may potentially be more susceptible to adverse health effects related to inhaled MWCNT. Hazard assessment of such inhaled nanomaterials therefore requires timely clarification. This was assessed in this study using a mouse model of COPD by exposing animals to 0.08 µg/cm 2 of MWCNT administered by intratracheal instillation. Treatment with MWCNT induced an accumulation of alveolar macrophages (AMφ) in bronchoalveolar lavage fluid (BALF) in COPD mice that increased from 24 h to 7 d. In COPD mice, MWCNT induced a dynamic shift in macrophage polarization as measured by expression of CD38 and CD206, and increased AMφ and lung parenchyma macrophage (LPMΦ) activation with upregulation of co-stimulatory markers CD40 and CD80. Moreover, MWCNT treatment increased the frequencies of pulmonary dendritic cells (DC), leading to an expansion of the CD11b + CD103 - DC subset. Although MWCNT did not trigger lung functional or structural changes, they induced an increased expression of the muc5AC transcript in mice with COPD. Our data provide initial evidence that inhaled MWCNT affect the pulmonary mucosal immune system by altering the numbers, phenotype, and activation status of antigen-presenting cell populations. Extrapolating these in vivo mouse findings to human pulmonary MWCNT exposure, caution is warranted in limiting exposure when handling inhalable nanofibers.

Background: Chronic obstructive pulmonary disease (COPD) has been associated with periodontal disease (PD), and periodontal treatment (PT) has been connected to reduction of lung disease exacerbations. Bronchiectasis has many clinical similarities with COPD but, although it is also a chronic lung disease, to date it has not been studied with relation to PD. The aim of this study is to evaluate whether PT associated with photodynamic therapy (PDT) reduces the number of exacerbations, improves pulmonary function, periodontal clinical parameters and quality of life after 1 year of periodontal treatment follow-up., Methods: Bronchiectasis patients will undergo medical anamnesis and periodontal examination. Participants with periodontitis will be divided into two groups and PT will be performed as G1 control group (n = 32) - OHO (oral hygiene orientation) + supragingival treatment + simulation of using photodynamic therapy (PDT); G2 experimental (n = 32) - scaling and root planing + PDT + OHO. Lung function will be assessed both at baseline and after 1 year by spirometry, exacerbation history will be analyzed through clinical records monitoring. Three instruments for quality of life assessment will also be applied - Saint George's Respiratory Questionnaire and Impact Profile Analysis Oral health (OHIP-14). It is expected that periodontal treatment can improve the analyzed parameters after 1 year., Discussion: Although only one study evaluates exacerbation in COPD after 1 year of PT, bronchiectasis has not been studied in the dentistry field to date., Trial Registration: NCT02514226. Version #1. This study protocol receives grant from FAPESP (São Paulo Research Foundation) #2015/20535-1. First received: July 22, 2015, 1 st version. This protocol has been approved by the Research Ethics Committee of Nove de Julho University.

Introduction: The association between periodontal disease (PD) and chronic obstructive pulmonary disease (COPD) has been widely studied, with aspiration of periodontal pathogens being one of the most accepted causal mechanisms for pulmonary exacerbation. Periodontal treatment (PT) was associated with a decrease in these exacerbations. Bronchiectasis is a pulmonary disease that has many similarities to COPD; however, there are no studies correlating this condition to PD thus far. This study will evaluate if PT reduces proinflammatory cytokines in serum and saliva, as well as halitosis and the amount of microorganisms associated with exacerbation of bronchiectasis in saliva, sputum and nasal lavage 3 months after PT., Methods and Analysis: A total of 182 patients with PD and bronchiectasis will be randomly allocated to group 1 (positive control; scaling and root planing (SRP)+oral hygiene (OH)) or group 2 (experimental; SRP+photodynamic therapy+OH). After 3 months, samples of saliva, nasal lavage and sputum will be collected to determine the level of Pseudomonas aeruginosa, Staphylococcus aureus and Porphyromonas gingivalis by quantitative PCR. This protocol will determine the efficacy of PT in reducing the most likely niches of bronchiectasis exacerbation by comparing pre- and post-treatment microbiology samples. Furthermore, there will be assessment of oral halitosis and verification of inflammatory cytokines in serum and saliva., Ethics and Dissemination: This protocol has been approved by the Research Ethics Committee of Universidade Nove de Julho. Data will be published in a peer-reviewed journal., Trial Registration Number: NCT02514226., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)