Modelling upper respiratory tract diseases: getting grips on host-microbe interactions in chronic rhinosinusitis using in vitro technologies

Rudder, Charlotte De; Calatayud, Marta; Lebeer, Sarah; Wiele, Tom Van de

doi:10.1186/s40168-018-0462-z

Cited by 19 publications

(13 citation statements)

References 127 publications

(136 reference statements)

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“…Most current upper respiratory tract model systems do not take into account such polymicrobial background and limit the number of microbial species that are in interaction with the host cells (23)(24)(25)(26)(27). We recently emphasized that a physiologically relevant model system of the sinonasal microenvironment requires both a representative epithelial structure and a microbial community that is characteristic for that of the human nose and sinuses (28). Charles et al (29) have incorporated these parameters in their model system and have developed an ex vivo nasal model that supports colonization of nasal bacteria on a cultured host mucosa created by immortalized human nasal epithelial cells.…”

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confidence: 99%

Dual and Triple Epithelial Coculture Model Systems with Donor-Derived Microbiota and THP-1 Macrophages To Mimic Host-Microbe Interactions in the Human Sinonasal Cavities

Rudder

Calatayud

Lebeer

et al. 2020

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The epithelium of the human sinonasal cavities is colonized by a diverse microbial community, modulating epithelial development and immune priming and playing a role in respiratory disease. Here, we present a novel in vitro approach enabling a 3-day coculture of differentiated Calu-3 respiratory epithelial cells with a donor-derived bacterial community, a commensal species (Lactobacillus sakei), or a pathobiont (Staphylococcus aureus). We also assessed how the incorporation of macrophage-like cells could have a steering effect on both epithelial cells and the microbial community. Inoculation of donor-derived microbiota in our experimental setup did not pose cytotoxic stress on the epithelial cell layers, as demonstrated by unaltered cytokine and lactate dehydrogenase release compared to a sterile control. Epithelial integrity of the differentiated Calu-3 cells was maintained as well, with no differences in transepithelial electrical resistance observed between coculture with donor-derived microbiota and a sterile control. Transition of nasal microbiota from in vivo to in vitro conditions maintained phylogenetic richness, and yet a decrease in phylogenetic and phenotypic diversity was noted. Additional inclusion and coculture of THP-1-derived macrophages did not alter phylogenetic diversity, and yet donor-independent shifts toward higher Moraxella and Mycoplasma abundance were observed, while phenotypic diversity was also increased. Our results demonstrate that coculture of differentiated airway epithelial cells with a healthy donor-derived nasal community is a viable strategy to mimic host-microbe interactions in the human upper respiratory tract. Importantly, including an immune component allowed us to study host-microbe interactions in the upper respiratory tract more in depth. IMPORTANCE Despite the relevance of the resident microbiota in sinonasal health and disease and the need for cross talk between immune and epithelial cells in the upper respiratory tract, these parameters have not been combined in a single in vitro model system. We have developed a coculture system of differentiated respiratory epithelium and natural nasal microbiota and incorporated an immune component. As indicated by absence of cytotoxicity and stable cytokine profiles and epithelial integrity, nasal microbiota from human origin appeared to be well tolerated by host cells, while microbial community composition remained representative for that of the human (sino)nasal cavity. Importantly, the introduction of macrophage-like cells enabled us to obtain a differential readout from the epithelial cells dependent on the donor microbial background to which the cells were exposed. We conclude that both model systems offer the means to investigate host-microbe interactions in the upper respiratory tract in a more representative way.

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confidence: 99%

Dual and Triple Epithelial Coculture Model Systems with Donor-Derived Microbiota and THP-1 Macrophages To Mimic Host-Microbe Interactions in the Human Sinonasal Cavities

Rudder

Calatayud

Lebeer

et al. 2020

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“…Among the existing models mimicking the nasal mucosa, none of them was fabricated through bioprinting. They are mainly presented by monolayers, air-fluid single or multilayered biointerfaces, and scaffold-based and explant-based cultures[ 110 ]. As the olfactory neuroepithelium located in the nasal mucosa is involved in virus entry and smell dysfunction[ 89 , 111 ], the rational model should contain sustentacular cells expressing high levels of ACE2 and TMPRSS2 and olfactory receptor neurons expressing these enzymes at lower levels.…”

Section: Designing An “Ideal” Tissue Model To Study Sars-cov-2 Infementioning

confidence: 99%

Engineering a Model to Study Viral Infections: Bioprinting, Microfluidics, and Organoids to Defeat Coronavirus Disease 2019 (COVID-19)

Shpichka¹,

Bikmulina²,

Peshkova³

et al. 2024

IJB

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While the number of studies related to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is constantly growing, it is essential to provide a framework of modeling viral infections. Therefore, this review aims to describe the background presented by earlier used models for viral studies and an approach to design an “ideal” tissue model for SARS-CoV-2 infection. Due to the previous successful achievements in antiviral research and tissue engineering, combining the emerging techniques such as bioprinting, microfluidics, and organoid formation are considered to be one of the best approaches to form in vitro tissue models. The fabrication of an integrated multi-tissue bioprinted platform tailored for SARS-CoV-2 infection can be a great breakthrough that can help defeat coronavirus disease in 2019.

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“…Further mechanistic studies are certainly needed to define the most important characteristics of candidate probiotic bacteria in the URT. At present, a standard model is lacking for in vitro URT adhesion assays (192), but several cell lines are used, such as A549 lung epithelial cells (193), Calu-3 human bronchial cells (194), FaDu hypopharyngeal cells (195), Detroit 562 pharyngeal cells (124), and CCl-23 laryngeal cells (196). In contrast to the interaction with the gut epithelium, mucosal adhesion of lactobacilli to the nasopharyngeal epithelium has not been extensively studied.…”

Section: Properties That Can Be Rationalized To Be Important For Urt mentioning

confidence: 99%

Translating Recent Microbiome Insights in Otitis Media into Probiotic Strategies

et al. 2019

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SUMMARY The microbiota of the upper respiratory tract (URT) protects the host from bacterial pathogenic colonization by competing for adherence to epithelial cells and by immune response regulation that includes the activation of antimicrobial and (anti-)inflammatory components. However, environmental or host factors can modify the microbiota to an unstable community that predisposes the host to infection or inflammation. One of the URT diseases most often encountered in children is otitis media (OM). The role of pathogenic bacteria like Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the pathogenesis of OM is well documented. Results from next-generation-sequencing (NGS) studies reveal other bacterial taxa involved in OM, such as Turicella and Alloiococcus. Such studies can also identify bacterial taxa that are potentially protective against URT infections, whose beneficial action needs to be substantiated in relevant experimental models and clinical trials. Of note, lactic acid bacteria (LAB) are members of the URT microbiota and associated with a URT ecosystem that is deemed healthy, based on NGS and some experimental and clinical studies. These observations have formed the basis of this review, in which we describe the current knowledge of the molecular and clinical potential of LAB in the URT, which is currently underexplored in microbiome and probiotic research.

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Modelling upper respiratory tract diseases: getting grips on host-microbe interactions in chronic rhinosinusitis using in vitro technologies

Cited by 19 publications

References 127 publications

Dual and Triple Epithelial Coculture Model Systems with Donor-Derived Microbiota and THP-1 Macrophages To Mimic Host-Microbe Interactions in the Human Sinonasal Cavities

Dual and Triple Epithelial Coculture Model Systems with Donor-Derived Microbiota and THP-1 Macrophages To Mimic Host-Microbe Interactions in the Human Sinonasal Cavities

Engineering a Model to Study Viral Infections: Bioprinting, Microfluidics, and Organoids to Defeat Coronavirus Disease 2019 (COVID-19)

Translating Recent Microbiome Insights in Otitis Media into Probiotic Strategies

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