Table 3.

Most common in vitro respiratory models to study host–pathogen interactions

Model type	Advantages	Disadvantages	In vitro example of host pathogen interaction	Cell type(s) used
Submerged cell line culture	–Easy to culture. –2–5 days culture period. –Less skill required. –Readily available/cheap.	–Representative of one cell type only. –Usually a cancerous cell line. –2D culture. –Not representative of air interface.	Respiratory syncytial virus[ 70 ]	Bronchial cell line (BEAS‐2B); Primary human nasal and bronchial epithelial cells.
ALI monoculture	–Representative of air interfaced condition found in vivo. –Permits the study of viral entrance and metabolic pathways apically and basally.	–More expensive. –3–4 weeks culture period with primary cells. –2D architecture.	SARS‐CoV[ 72 ]	Primary human alveolar type II cells.
			SARS‐CoV[ 92 ]	Calu‐3 cell line.
ALI co‐culture	–Most biomimetic static cell culture available. –Representative of multiple cell types and systems found in vivo. –2.5D architecture.	–High level of skill needed to culture. –4–6 weeks culture period with primary cells.	Aspergillus (A.) fumigatus [ 73 ]	Human primary bronchial epithelial cells, small airway cells, human blood derived macrophages, and dendritic cells.
Polymer scaffolds	–Ability to house multiple cell types. –3D architecture.	–High level of skill and precision needed to slice and culture. –Difficulty in monitoring cells within structure.	Influenza A[ 115 ]	Human primary small epithelial cells.
			Papain (mimics air bourne allergen)[ 81 ]	Calu‐3 epithelial cell line, MRC‐5 fibroblast cell line, blood‐derived dendritic cells.
Organoids	–Derived from stem cells. –Representative of the integrated tissue found in vivo. –3D structure.	–High level of skill needed to culture. –3–5 weeks culture period. –Cant access/monitor apical and internal cell types without disrupting.	Parainfluenza[ 86 ]	Human embryonic stem cells.
			Respiratory syncytial virus[ 85 ]	Human embryonic stem cells.
			Multiple emerging influenza virus[ 91 ]	Tissue resident adult stem cells.
Precision cut lung slices (PCLS)	–Fully differentiated tissue. –Representative of the heterogeneous phenotypes of population. –3D architecture. –Culture times are less than that of ALI culture.	–High level of skill and precision needed to slice and culture. –Expensive and limited supply.	Influenza[ 88 ]	Healthy lung slices from cancer patients undergoing lung resection.
			Rhinovirus[ 89 ]	Healthy and asthmatic lung slices from patient donors.
			LPS (mimics bacterial infection)[ 90 ]	Lung slices from patients with a variety of medical conditions from the National Disease Research Interchange.

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