Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 100, Issue 5, Pages 985-997Publisher
OXFORD UNIV PRESS
DOI: 10.1189/jlb.4VMR0316-103R
Keywords
respiratory infections; immunity; oxidized phospholipids; n-3 PUFAs
Categories
Funding
- U.S. National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIH/NIEHS) [Z01 ES102005]
- NIH, National Institute of Complementary and Integrative Health [R01AT008375]
- Health Effects Institute Walter Rosenblith Award
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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.
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