ORCID Profile
0000-0001-7462-2054
Current Organisation
University of Oxford
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Publisher: Elsevier BV
Date: 02-2020
Publisher: American Thoracic Society
Date: 05-2019
Publisher: American Society for Clinical Investigation
Date: 04-2022
DOI: 10.1172/JCI157124
Publisher: European Respiratory Society (ERS)
Date: 31-03-2022
DOI: 10.1183/23120541.00586-2021
Abstract: Streptococcus pneumoniae (pneumococcus) is the most commonly identified bacterial cause of pneumonia and the leading infectious cause of death in children under 5 years of age worldwide. Pneumococcal disease follows a seasonal pattern with increased incidence during winter. Pneumonia burden is also associated with poor air quality. Nasopharyngeal carriage of the bacterium is a pre-requisite of invasive disease. We aimed to determine if susceptibility to nasopharyngeal pneumococcal carriage varied by season and which environmental factors might explain such variation. We also evaluated the influence of sex on susceptibility of carriage. We collated data from five studies in which human volunteers underwent intranasal pneumococcal challenge. Generalised linear mixed-effects models were used to identify factors associated with altered risk of carriage acquisition, specifically climate and air-quality data. During 2011–2017, 374 healthy adults were challenged with type 6B pneumococcus. Odds of carriage were significantly lower in males (OR, 0.61 95% CI, 0.40–0.92 p=0.02), and higher with cooler temperatures (OR, 0.79 95% CI, 0.63–0.99 p=0.04). Likelihood of carriage was also associated with lower concentrations of local fine particulate matter concentrations (PM 2.5 ) and increased local rainfall. In contrast to epidemiological series, experimental challenge allowed us to test propensity to acquisition during controlled exposures immunological explanations for sex and climatic differences should be sought.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2019
Publisher: American Society for Microbiology
Date: 23-02-2021
Abstract: Occurrence of lower respiratory tract infections requires prior colonization of the upper respiratory tract with a pathogen. Most bacterial infection and colonization studies have been performed in murine and in vitro models due to the current invasive s ling methodology of the upper respiratory tract, both of which poorly reflect the complexity of host-pathogen interactions in the human nose.
Publisher: American Society for Clinical Investigation
Date: 26-01-2021
Publisher: American Society for Clinical Investigation
Date: 03-10-2011
DOI: 10.1172/JCI44254
Publisher: American Thoracic Society
Date: 03-2021
Publisher: American Society for Clinical Investigation
Date: 16-09-2019
DOI: 10.1172/JCI128865
Publisher: American Society for Microbiology
Date: 16-12-2020
DOI: 10.1128/AAC.01468-20
Abstract: Cefepime-enmetazobactam is a novel β-lactam–β-lactamase inhibitor combination with broad-spectrum antimicrobial activity against a range of multidrug-resistant Enterobacteriaceae . This agent is being developed for a range of serious hospital infections. An understanding of the extent of partitioning of β-lactam–β-lactamase inhibitor combinations into the human lung is required to better understand the potential role of cefepime-enmetazobactam for the treatment of nosocomial pneumonia.
Publisher: American Thoracic Society
Date: 12-2022
Publisher: Cold Spring Harbor Laboratory
Date: 29-04-2020
DOI: 10.1101/2020.04.23.20077073
Abstract: Pneumococcal colonisation is key to the pathogenesis of invasive disease, but is also immunogenic in young adults, protecting against re-colonisation. Colonisation is rarely detected in older adults, despite high rates of pneumococcal disease. To establish experimental human pneumococcal colonisation in healthy adults aged 50—84 years, to measure the immune response to pneumococcal challenge, and to assess the protective effect of prior colonisation against autologous strain rechallenge. Sixty-four participants were inoculated with Streptococcus pneumoniae (serotype 6B, 80,000CFU in each nostril). Colonisation was determined by bacterial culture of nasal wash, serum anti-6B capsular IgG responses by ELISA, and anti-protein immune responses by multiplex electrochemiluminescence. Experimental colonisation was established in 39% of participants (25/64) with no adverse events. Colonisation occurred in 47% (9/19) of participants aged 50—59 compared with 21% (3/14) in those aged ≥70 years. Previous pneumococcal polysaccharide vaccination did not protect against colonisation. Colonisation did not confer serotype-specific immune boosting: GMT (95% CI) 2.7μg/mL (1.9—3.8) pre-challenge versus 3.0 (1.9—4.7) four weeks post-colonisation (p = 0.53). Furthermore, pneumococcal challenge without colonisation led to a drop in specific antibody levels from 2.8μg/mL (2.0—3.9) to 2.2μg/mL (1.6—3.0) post-challenge (p = 0.006). Anti-protein antibody levels increased following successful colonisation. Rechallenge with the same strain after a median of 8.5 months (IQR 6.7—10.1) led to recolonisation in 5/16 (31%). In older adults, experimental pneumococcal colonisation is feasible and safe, but demonstrates different immunological outcomes compared with younger adults in previous studies.
Publisher: American Thoracic Society
Date: 02-2020
Publisher: Springer Science and Business Media LLC
Date: 29-10-2018
Publisher: Elsevier BV
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 16-07-2019
DOI: 10.1038/S41467-019-11005-2
Abstract: Control of Streptococcus pneumoniae colonisation at human mucosal surfaces is critical to reducing the burden of pneumonia and invasive pneumococcal disease, interrupting transmission, and achieving herd protection. Here, we use an experimental human pneumococcal carriage model (EHPC) to show that S. pneumoniae colonisation is associated with epithelial surface adherence, micro-colony formation and invasion, without overt disease. Interactions between different strains and the epithelium shaped the host transcriptomic response in vitro. Using epithelial modules from a human epithelial cell model that recapitulates our in vivo findings, comprising of innate signalling and regulatory pathways, inflammatory mediators, cellular metabolism and stress response genes, we find that inflammation in the EHPC model is most prominent around the time of bacterial clearance. Our results indicate that, rather than being confined to the epithelial surface and the overlying mucus layer, the pneumococcus undergoes micro-invasion of the epithelium that enhances inflammatory and innate immune responses associated with clearance.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Jesús Reiné.