Infection Studies with Airway Organoids from Carollia perspicillata Indicate That the Respiratory Epithelium Is Not a Barrier for Interspecies Transmission of Influenza Viruses

Abstract

We developed an organoid culture system derived from the airways of the bat species Carollia perspicillata . Using this cell system, we showed that the airway epithelium of these bats is highly susceptible to infection by influenza viruses of other mammalian species and thus is not a barrier for interspecies transmission.

Reconstructing bat antiviral immunity using epithelial organoids

“…One exception were airway goblet cells, which were of low abundance but could be readily induced by IL-13 stimulation. These findings are consistent with a recent report on tracheal organoids from Eonycteris spelaea 36 and Carollia perspicillata 37 , suggesting that external factors present in vivo control airway goblet cell formation and maintenance. Single-cell RNA profiling further identified rare cell types that include lung microfold cells (M-cells), which specialize in luminal antigen uptake and presentation to intraepithelial immune cells.…”

“…Expanding nasal, tracheal, and distal lung KRT5+ basal cell organoids displayed a compact morphology and upon differentiation formed a lumen with inwards facing beating cilia (Figure 1F, Supplemental Figure S1B, Supplemental movie 1). These structures are highly reminiscent of human nasal and large airway organoids as well as bat tracheal organoids established previously 36, 37, 44, 46 . Basal cell airway organoids from the upper (nose) and lower (trachea, conducting airways) respiratory tract could be expanded for more than 6 months and retained prototypic transcription factor expression in vitro , such as SIX3 for the upper and IRX2 for the lower airway 47 (Supplemental Figure S1C).…”

“…In humans, stem cell-derived organoids have been used extensively to assess key aspects of virus infections, host cell responses, or to test drugs and vaccines 32 . A small number of bat organoids has been established so far, including intestinal organoids from Rhinolophus sinicus 33 , Artibeus jamaicensis 34 and Rousettus leschenaultii 35 , as well as tracheal organoids from Eonycteris spelaea 36 and Carollia perspicillata 37 . However, these pioneering studies have critically lacked any in depth molecular characterization and functional genetic perturbations of naïve or infected organoids, likely due to limitation in fully annotated reference genomes.…”

Infection of porcine enteroids and 2D differentiated intestinal epithelial cells with rotavirus A to study cell tropism and polarized immune response

“…2D monolayers were fixed in 10% neutral-buffered formalin, as described previously. After embedding in paraffin, the samples were sectioned at 2 μm thickness and prepared for haematoxylin and eosin (H&E) and IHC staining using a standard protocol [ 40 , 41 ]. To localize the distribution of enterocyte in 2D differentiated intestinal epithelia cells, antibody specific for Villin was used.…”

Mapping the scientific output of organoids for modeling animal and human infectious diseases: A bibliometric assessment

“…Notably, a considerable number of organoids from other animals were quickly incorporated into infectious disease research upon development. Speci cally, chiropteran airways [75] and intestinal organoids [76] have been developed to study the SARS-CoV-2 virus, given the suspected origin of COVID-19 in bats. Recent years have marked a notable increase in the development of animal organoids, signifying rapid advances in the establishment of animal organoids and their utilization in infectious disease research.…”