Role for phospholipid acyl chains and cholesterol in pulmonary infections and inflammation

Abstract

Bacterial and viral respiratory tract infections result in millions of deaths worldwide and are currently the leading cause of death from infection. Acute inflammation is an essential element of host defense against infection, but can be damaging to the host when left unchecked. Effective host defense requires multiple lipid mediators, which collectively have proinflammatory and/or proresolving effects on the lung. During pulmonary infections, phospholipid acyl chains and cholesterol can be chemically and enzymatically oxidized, as well as truncated and modified, producing complex mixtures of bioactive lipids. We review recent evidence that phospholipids and cholesterol and their derivatives regulate pulmonary innate and adaptive immunity during infection. We first highlight data that oxidized phospholipids generated in the lung during infection stimulate pattern recognition receptors, such as TLRs and scavenger receptors, thereby amplifying the pulmonary inflammatory response. Next, we discuss evidence that oxidation of endogenous pools of cholesterol during pulmonary infections produces oxysterols that also modify the function of both innate and adaptive immune cells. Last, we conclude with data that n-3 polyunsaturated fatty acids, both in the form of phospholipid acyl chains and through enzymatic processing into endogenous proresolving lipid mediators, aid in the resolution of lung inflammation through distinct mechanisms. Unraveling the complex mechanisms of induction and function of distinct classes of bioactive lipids, both native and modified, may hold promise for developing new therapeutic strategies for improving pulmonary outcomes in response to infection.

Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work

“…As reported by Imai et al, oxPL-induced inflammation is mediated by TLR4 and TRIF, driving an increase in IL-6 production [89]. It is intriguing to consider that oxPL-dependent defects in phagocytosis and ROS generation may lead to an increased susceptibility to respiratory infections [90]. Cholesterol is the major neutral lipid in pulmonary surfactant, in which it is thought to promote the spreading, mobility, and adsorption of surfactant films [91].…”

Serum, plasma and erythrocyte membrane lipidomes in infants fed formula supplemented with bovine milk fat globule membranes

“…36 With respect to immunological effects, it is known that PLs play an important role in modulating gut inflammation, 37 and also affect the inflammatory response in the lungs during pulmonary infection. 38 Sphingolipid metabolites, Cer, and sphingosine-1phosphate, regulate immune cell trafficking and epithelial integrity and therefore are important in inflammation and inflammatory diseases. 30 Changes in SM and its metabolite Cer affect T-cell response, both in early activation steps and effector functions.…”

An Updated Overview of Metabolomic Profile Changes in Chronic Obstructive Pulmonary Disease

“…Lyso-phospholipids can cause dysfunction of vascular endothelial cells by activating NF-κB and promoting inflammatory cytokine production from leukocytes [76]. In addition, increased oxidative stress in COPD can promote the oxidation of phospholipids and activate the innate immune system, resulting in persistent inflammation [77].…”