The crosstalk between respiratory pathogens and the host: the alveolar homeostasis in the face of the enemy
The process of breathing is realized in a highly specialized system, the alveolus. The fragile alveolar homeostasis is challenged during life by numerous respiratory pathogens resulting in epithelial and endothelial damage, barrier disruption, and robust inflammatory response. Nevertheless, various host defense strategies preserve this balance by immune cell migration and the expression of specific substances. However, these processes can be strongly influenced by important comorbidity factors, e.g., obesity and aging.
The host-pathogen crosstalk can be investigated by using different model systems. Considerable progress has been made in this area in recent years; organoids, the alveolus-on-a-chip, and humanized mouse models are available to figure out the pathomechanisms behind the infection.
Own data demonstrate that especially bacterial co-infections in the context of viral disease lead to severe barrier damage and that inhibitors of intracellular signaling processes can result in a sufficient inhibition of virus replication. The current COVID-19 pandemic demonstrates clearly that host factors such as senescence can lead to an increased susceptibility, which, due to the broad organ tropism of SARS-COV-2, can also result in damage outside the lung.
Using sophisticated technologies, system biology can improve the understanding of the interplay between pathogens and the host to establish new solutions against our enemies.