Research progress of lung organoids in infectious respiratory diseases

Infectious respiratory diseases are common epidemics that often exhibit phased outbreaks, increasing the healthcare burden. Past research models for these diseases were relatively simplistic, but the emergence of organoids has transformed this landscape. Organoids, three-dimensional in vitro tissue analogs that recapitulate specific spatial organ structures derived from stem cell culture, have advanced significantly over the decade since their inception. Compared to conventional animal models, organoids circumvent interspecies variations, enabling a more precise representation of human physiological and pathological traits. Relative to two-dimensional cell cultures, organoids exhibit enhanced complexity, incorporating diverse cell types and maintaining stable genomes, which facilitates a more faithful simulation of cellular interactions within the extracellular microenvironment. Consequently, as a three-dimensional in vitro model, lung organoids are pivotal for investigating lung organ development, infectious disease pathogenesis, and drug screening. Although SARS-CoV-2 is receding from the spotlight, advancing lung organoid development for addressing infectious respiratory diseases like influenza remains a priority. This review demonstrated the differentiation culture process of lung organoids and outlined advancements in utilizing organoids to elucidate pathogenic infection mechanisms, reveal virus-host interactions and screen therapeutic drugs over the past seven years. Additionally, we have summarized the advances in lung organoid model technologies and outlined their developmental directions.