Influenza A virus selectively elevates prostaglandin E2 formation in pro-resolving macrophages
Paul M. Jordan,
Kerstin Günther,
Vivien Nischang,
Yuping Ning,
Stefanie Deinhardt-Emmer,
Christina Ehrhardt,
Oliver Werz
Affiliations
Paul M. Jordan
Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Philosophenweg 14, 07743 Jena, Germany; Jena Center for Soft Matter (JCSM); Friedrich Schiller University Jena, Philosophenweg 7, 07743 Jena, Germany; Corresponding author
Kerstin Günther
Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Philosophenweg 14, 07743 Jena, Germany
Vivien Nischang
Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Philosophenweg 14, 07743 Jena, Germany
Yuping Ning
Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Philosophenweg 14, 07743 Jena, Germany
Stefanie Deinhardt-Emmer
Institute of Medical Microbiology, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany
Christina Ehrhardt
Section of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knoell-Str. 2, 07745 Jena, Germany
Oliver Werz
Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Philosophenweg 14, 07743 Jena, Germany; Jena Center for Soft Matter (JCSM); Friedrich Schiller University Jena, Philosophenweg 7, 07743 Jena, Germany; Corresponding author
Summary: Respiratory influenza A virus (IAV) infections are major health concerns worldwide, where bacterial superinfections substantially increase morbidity and mortality. The underlying mechanisms of how IAV impairs host defense remain elusive. Macrophages are pivotal for the innate immune response and crucially regulate the entire inflammatory process, occurring as inflammatory M1- or pro-resolving M2-like phenotypes. Lipid mediators (LM), produced from polyunsaturated fatty acids by macrophages, are potent immune regulators and impact all stages of inflammation. Using LM metabololipidomics, we show that human pro-resolving M2-macrophages respond to IAV infections with specific and robust production of prostaglandin (PG)E2 along with upregulation of cyclooxygenase-2 (COX-2), which persists after co-infection with Staphylococcus aureus. In contrast, cytokine/interferon production in macrophages was essentially unaffected by IAV infection, and the functionality of M1-macrophages was not influenced. Conclusively, IAV infection of M2-macrophages selectively elevates PGE2 formation, suggesting inhibition of the COX-2/PGE2 axis as strategy to limit IAV exacerbation.
