Impact of Bacterial Toxins in the Lungs.

Bacterial toxins play a key role in the pathogenesis of lung disease. Based on their structural and functional properties, they employ various strategies to modulate lung barrier function and to impair host defense in order to promote infection. Although in general, these toxins target common cellular signaling pathways and host compartments, toxin- and cell-specific effects have also been reported. Toxins can affect resident pulmonary cells involved in alveolar fluid clearance (AFC) and barrier function through impairing vectorial Na+ transport and through cytoskeletal collapse, as such, destroying cell-cell adhesions. The resulting loss of alveolar-capillary barrier integrity and fluid clearance capacity will induce capillary leak and foster edema formation, which will in turn impair gas exchange and endanger the survival of the host. Toxins modulate or neutralize protective host cell mechanisms of both the innate and adaptive immunity response during chronic infection. In particular, toxins can either recruit or kill central players of the lung's innate immune responses to pathogenic attacks, i.e., alveolar macrophages (AMs) and neutrophils. Pulmonary disorders resulting from these toxin actions include, e.g., acute lung injury (ALI), the acute respiratory syndrome (ARDS), and severe pneumonia. When acute infection converts to persistence, i.e., colonization and chronic infection, lung diseases, such as bronchitis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) can arise. The aim of this review is to discuss the impact of bacterial toxins in the lungs and the resulting outcomes for pathogenesis, their roles in promoting bacterial dissemination, and bacterial survival in disease progression.

Phosphatidylglycerol and surfactant: A potential treatment for COVID-19?

A hypothesis concerning the potential utility of surfactant supplementation for the treatment of critically ill patients with COVID-19 is proposed, along with a brief summary of the data in the literature supporting this idea. It is thought that surfactant, which is already approved by the Food and Drug Administration for intratracheal administration to treat neonatal respiratory distress syndrome in pre-term infants, could benefit COVID-19-infected individuals by: (1) restoring surfactant damaged by lung infection and/or decreased due to the virus-induced death of the type II pneumocytes that produce it and (2) reducing surface tension to decrease the work of breathing and limit pulmonary edema. In addition, a constituent of surfactant, phosphatidylglycerol, could mitigate COVID-19-induced lung pathology by: (3) decreasing excessive innate immune system stimulation via its inhibition of toll-like receptor-2 and -4 activation by microbial components and cellular proteins released by damaged cells, thereby limiting inflammation and the resultant pulmonary edema, and (4) possibly blocking spread of the viral infection to non-infected cells in the lung. Therefore, it is suggested that surfactant preparations containing phosphatidylglycerol be tested for their ability to improve lung function in critically ill patients with COVID-19.