The Role of Lipids in the Crosstalk Between Lung Structural Cells and Innate Immune Cells During Respiratory Infection

Despite intensive research on pulmonary immunity, the COVID-19 pandemics highlighted our incomplete knowledge of how the lung responds to infection. To ensure pulmonary functions during infection, host cells must communicate to maintain the delicate balance between elimination of the pathogen and control of lung damage. Both immune and structural cells contribute to creating a microenvironment that shapes their phenotype and function. However, the mediators involved in those processes are still unclear. Growing evidence identifies lipids as key regulators of pulmonary homeostasis, mediating both physiological and pathophysiological processes in the lungs. They participate in surfactant metabolism and regulation of innate and adaptive responses. Importance of the surfactant homeostasis is highlighted in pulmonary alveolar proteinosis where macrophage dysfunction led to lipids accumulation, impaired lung function and increased susceptibility to infection. Interestingly, lipid-lowering drugs, such as statins, increase cholesterol clearance from alveolar macrophages and improve respiratory functions. The term “lipids” includes various host mediators, such as the phospholipids, the bioactive lipids, i.e. eicosanoids involved in the induction and resolution of inflammation, but also lipoproteins, involved in bacterial clearance. In addition, fatty acid synthesis and oxidation are also an important piece of the puzzle to understand pulmonary diseases. Microbial lipids are also important actors of pulmonary response to infection in addition to host lipids. However, the role of those mediators in the immune-structural cells interaction remain poorly defined.

In this Research Topic, we aim to study the role of the host lipids in the interaction between lung structural and innate immune cells. We believe that understanding the function of the lipid mediators will lead to the identification of new therapeutic avenues. For this purpose, research using ex vivo/in vitro models (such as lung organoids or multicellular co-culture systems), genetically engineered murine models or lipidomic analyses will allow the manipulation and identification of the lipids functions in respiratory diseases. Importantly, we aim to highlight the therapeutic potential of using and/or targeting lipids during respiratory infection.

We welcome studies regarding lipid mediators, lipoproteins, phospholipids and lipid metabolism involved in lung responses to infection. We encourage the submission of Original Research, Method, Mini Review, or other types of articles, focusing on, but not limited to, the following subtopics:

• How pulmonary structural cells shape the innate immune response.
• How innate immune cells influence the response of lung structural cells.
• Cell types involved in the response to lipids.
• Role of the pulmonary surfactant, pro-resolving mediators, low- and high-density lipoproteins during infection.
• Importance of the location of the immune response (upper vs lower airways) for disease outcome.
• Use of lipids as a therapeutic approach.
• Manipulating the host lipid metabolism to enhance the clearance of the pathogen or limit immunopathology: new perspective?