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Fast-track development of an in vitro 3D lung/immune cell model to study Aspergillus infections.

ABSTRACT: To study interactions of airborne pathogens, e.g. Aspergillus (A.) fumigatus with upper and lower respiratory tract epithelial and immune cells, we set up a perfused 3D human bronchial and small airway epithelial cell system. Culturing of normal human bronchial or small airway epithelial (NHBE, SAE) cells under air liquid interphase (ALI) and perfusion resulted in a significantly accelerated development of the lung epithelia associated with higher ciliogenesis, cilia movement, mucus-production and improved barrier function compared to growth under static conditions. Following the accelerated differentiation under perfusion, epithelial cells were transferred into static conditions and antigen-presenting cells (APCs) added to study their functionality upon infection with A. fumigatus. Fungi were efficiently sensed by apically applied macrophages or basolaterally adhered dendritic cells (DCs), as illustrated by phagocytosis, maturation and migration characteristics. We illustrate here that perfusion greatly improves differentiation of primary epithelial cells in vitro, which enables fast-track addition of primary immune cells and significant shortening of experimental procedures. Additionally, co-cultured primary DCs and macrophages were fully functional and fulfilled their tasks of sensing and sampling fungal pathogens present at the apical surface of epithelial cells, thereby promoting novel possibilities to study airborne infections under conditions mimicking the in vivo situation.

SUBMITTER: Chandorkar P

PROVIDER: S-EPMC5599647 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Fast-track development of an in vitro 3D lung/immune cell model to study Aspergillus infections.

Chandorkar P P Posch W W Zaderer V V Blatzer M M Steger M M Ammann C G CG Binder U U Hermann M M Hörtnagl P P Lass-Flörl C C Wilflingseder D D

Scientific reports 20170914 1

To study interactions of airborne pathogens, e.g. Aspergillus (A.) fumigatus with upper and lower respiratory tract epithelial and immune cells, we set up a perfused 3D human bronchial and small airway epithelial cell system. Culturing of normal human bronchial or small airway epithelial (NHBE, SAE) cells under air liquid interphase (ALI) and perfusion resulted in a significantly accelerated development of the lung epithelia associated with higher ciliogenesis, cilia movement, mucus-production a ...[more]

PMID: 28912507

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Project description:BackgroundMore than 300 cities including the city of Amsterdam in the Netherlands have joined the UNAIDS Fast-Track Cities initiative, committing to accelerate their HIV response and end the AIDS epidemic in cities by 2030. To support this commitment, we aimed to estimate the number and proportion of Amsterdam HIV infections that originated within the city, from Amsterdam residents. We also aimed to estimate the proportion of recent HIV infections during the 5-year period 2014-2018 in Amsterdam that remained undiagnosed.MethodsWe located diagnosed HIV infections in Amsterdam using postcode data (PC4) at time of registration in the ATHENA observational HIV cohort, and used HIV sequence data to reconstruct phylogeographically distinct, partially observed Amsterdam transmission chains. Individual-level infection times were estimated from biomarker data, and used to date the phylogenetically observed transmission chains as well as to estimate undiagnosed proportions among recent infections. A Bayesian Negative Binomial branching process model was used to estimate the number, size, and growth of the unobserved Amsterdam transmission chains from the partially observed phylogenetic data.ResultsBetween 1 January 2014 and 1 May 2019, there were 846 HIV diagnoses in Amsterdam residents, of whom 516 (61%) were estimated to have been infected in 2014-2018. The rate of new Amsterdam diagnoses since 2014 (104 per 100,000) remained higher than the national rates excluding Amsterdam (24 per 100,000), and in this sense Amsterdam remained a HIV hotspot in the Netherlands. An estimated 14% [12-16%] of infections in Amsterdan MSM in 2014-2018 remained undiagnosed by 1 May 2019, and 41% [35-48%] in Amsterdam heterosexuals, with variation by region of birth. An estimated 67% [60-74%] of Amsterdam MSM infections in 2014-2018 had an Amsterdam resident as source, and 56% [41-70%] in Amsterdam heterosexuals, with heterogeneity by region of birth. Of the locally acquired infections, an estimated 43% [37-49%] were in foreign-born MSM, 41% [35-47%] in Dutch-born MSM, 10% [6-18%] in foreign-born heterosexuals, and 5% [2-9%] in Dutch-born heterosexuals. We estimate the majority of Amsterdam MSM infections in 2014-2018 originated in transmission chains that pre-existed by 2014.ConclusionsThis combined phylogenetic, epidemiologic, and modelling analysis in the UNAIDS Fast-Track City Amsterdam indicates that there remains considerable potential to prevent HIV infections among Amsterdam residents through city-level interventions. The burden of locally acquired infection remains concentrated in MSM, and both Dutch-born and foreign-born MSM would likely benefit most from intensified city-level interventions.FundingThis study received funding as part of the H-TEAM initiative from Aidsfonds (project number P29701). The H-TEAM initiative is being supported by Aidsfonds (grant number: 2013169, P29701, P60803), Stichting Amsterdam Dinner Foundation, Bristol-Myers Squibb International Corp. (study number: AI424-541), Gilead Sciences Europe Ltd (grant number: PA-HIV-PREP-16-0024), Gilead Sciences (protocol numbers: CO-NL-276-4222, CO-US-276-1712, CO-NL-985-6195), and M.A.C AIDS Fund.

Dataset Information

Fast-track development of an in vitro 3D lung/immune cell model to study Aspergillus infections.

Publications

Fast-track development of an in vitro 3D lung/immune cell model to study Aspergillus infections.

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