In Vitro Models for Studying Respiratory Host–Pathogen Interactions

Abstract

Respiratory diseases and lower respiratory tract infections are among the leading cause of death worldwide and, especially given the recent severe acute respiratory syndrome coronavirus‐2 pandemic, are of high and prevalent socio‐economic importance. In vitro models, which accurately represent the lung microenvironment, are of increasing significance given the ethical concerns around animal work and the lack of translation to human disease, as well as the lengthy time to market and the attrition rates associated with clinical trials. This review gives an overview of the biological and immunological components involved in regulating the respiratory epithelium system in health, disease, and infection. The evolution from 2D to 3D cell biology and to more advanced technological integrated models for studying respiratory host–pathogen interactions are reviewed and provide a reference point for understanding the in vitro modeling requirements. Finally, the current limitations and future perspectives for advancing this field are presented.

Epithelial uptake ofAspergillus fumigatusdrives efficient fungal clearancein vivoand is aberrant in Chronic Obstructive Pulmonary Disease (COPD)

“…While bacteria and virus represent the largest causes of exacerbations in COPD patients, accounting for approximately 70% of cases[86], fungal pathogens, such as Af, are becoming increasingly recognised as an important etiological cause of exacerbations. Notably, exacerbations due to respiratory infections are the cause of a significant proportion of the morbidity and mortality associated with COPD, which is listed by the World Health Organisation (WHO) as the third leading cause of death in the world, causing over 3 million deaths globally a year.Prevention of exacerbations would thus represent a key strategy for the clinical management of COPD[87][88][89]; however, our current understanding of the mechanisms underlying the increased susceptibility of these patients to respiratory infections are limited due to the inherent heterogeneity of COPD and the lack of standardised and high-throughput in vitro and in vivo models of disease[90][91][92][93]. The development of a highly controlled in vitro Af infection model exploiting commercially available and locally-sourced primary human AECs from healthy donors and COPD patients has allowed us to start deciphering the mechanisms underlying the increased susceptibility of COPD patients to fungal infections.…”

Modeling Crevicular Fluid Flow and Host‐Oral Microbiome Interactions in a Gingival Crevice‐on‐Chip

“…These events are secondary to the design of the monolayer and 3D organotypic culture systems which limits the scope of recapitulating microbial colonization seen in the gingival crevice. [61][62][63] The gingival crevice-on-chip model described here enables stable and long-term host-microbe co-culture because of the compartmentalization and presence of continuous fluid flow that simulates the role of GCF. Second, the continuous flow of media overcomes the limitations related to nutrient depletion and metabolic waste accumulation.…”

Respiratory Epithelial Cells: More Than Just a Physical Barrier to Fungal Infections

“…A promising strategy consists of in vitro cell culture systems (such as air liquid interface, polymer scaffolds, and organoids—see ref. [ 98 ] for review) that are more closely related to the in vivo respiratory system, which may help researchers discover new therapeutic approaches for respiratory infectious diseases.…”