{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:06:53Z","timestamp":1770833213085,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T00:00:00Z","timestamp":1584489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK1870"],"award-info":[{"award-number":["GRK1870"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mecklenburg-Pomerania Excellence Initiative (Germany) and European Social Fund (ESF)","award":["ESF_14-BM-A55-00xx_16"],"award-info":[{"award-number":["ESF_14-BM-A55-00xx_16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Respiratory tract infections are a global health problem. The main causative agents of these infections are influenza A virus (IAV), Staphylococcus aureus (S. aureus), and Streptococcus pneumoniae (S. pneumoniae). Major research focuses on genetics and immune responses in these infections. Eicosanoids and other oxylipins are host-derived lipid mediators that play an important role in the activation and resolution of inflammation. In this study, we assess, for the first time, the different intracellular profiles of these bioactive lipid mediators during S. aureus LUG2012, S. pneumoniae TIGR4, IAV, and corresponding viral and bacterial co-infections of 16HBE cells. We observed a multitude of altered lipid mediators. Changes in the amount of 5-hydroxyeicosatetraenoic acid (5-HETE) were prominent for all bacterial infections. The infection with S. pneumoniae showed the strongest impact on bioactive lipid production and led to alterations in the amount of PPAR\u03b3 ligands and precursors of pro-resolving lipid mediators.<\/jats:p>","DOI":"10.3390\/metabo10030113","type":"journal-article","created":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T10:01:35Z","timestamp":1584612095000},"page":"113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["16HBE Cell Lipid Mediator Responses to Mono and Co-Infections with Respiratory Pathogens"],"prefix":"10.3390","volume":"10","author":[{"given":"Daniel","family":"Schultz","sequence":"first","affiliation":[{"name":"Institute of Biochemistry, University of Greifswald, 17487 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2683-2350","authenticated-orcid":false,"given":"Surabhi","family":"Surabhi","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Infection Biology, University of Greifswald, 17487 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Stelling","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Infection Biology, University of Greifswald, 17487 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Rothe","sequence":"additional","affiliation":[{"name":"Lipidomix, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"KoInfekt Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Methling","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, University of Greifswald, 17487 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6382-6681","authenticated-orcid":false,"given":"Sven","family":"Hammerschmidt","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Infection Biology, University of Greifswald, 17487 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolai","family":"Siemens","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Infection Biology, University of Greifswald, 17487 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9230-0267","authenticated-orcid":false,"given":"Michael","family":"Lalk","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, University of Greifswald, 17487 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/S0140-6736(18)32203-7","article-title":"Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"Roth","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S2213-2600(18)30496-X","article-title":"Mortality, morbidity, and hospitalisations due to influenza lower respiratory tract infections, 2017: An analysis for the Global Burden of Disease Study 2017","volume":"7","author":"Reiner","year":"2019","journal-title":"Lancet Respir. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3810\/pgm.2013.11.2710","article-title":"The Changing Microbiologic Epidemiology of Community-Acquired Pneumonia","volume":"125","author":"Aliberti","year":"2013","journal-title":"Postgrad. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrmicro3231","article-title":"The co-pathogenesis of influenza viruses with bacteria in the lung","volume":"12","author":"McCullers","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.cell.2013.05.052","article-title":"Lipidomic profiling of influenza infection identifies mediators that induce and resolve inflammation","volume":"154","author":"Tam","year":"2013","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.1172\/JCI97951","article-title":"Key roles for lipid mediators in the adaptive immune response","volume":"128","author":"Duffney","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cell.2013.06.024","article-title":"Lessons from lipids in the fight against influenza","volume":"154","year":"2013","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.smim.2013.08.006","article-title":"Lipidomic profiling of bioactive lipids by mass spectrometry during microbial infections","volume":"25","author":"Tam","year":"2013","journal-title":"Semin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/jb\/mvs092","article-title":"Mediator lipidomics in acute inflammation and resolution","volume":"152","author":"Arita","year":"2012","journal-title":"J. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8176","DOI":"10.1021\/ac1015563","article-title":"Comprehensive Lipidomics Analysis of Bioactive Lipids in Complex Regulatory Networks","volume":"82","author":"Masoodi","year":"2010","journal-title":"Anal. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature13479","article-title":"Pro-resolving lipid mediators are leads for resolution physiology","volume":"510","author":"Serhan","year":"2014","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1146\/annurev.ph.54.030192.001511","article-title":"Arachidonic acid metabolism in airway epithelial cells","volume":"54","author":"Holtzman","year":"1992","journal-title":"Annu. Rev. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1111\/j.1365-2222.2006.02498.x","article-title":"Cysteinyl leukotrienes: Multi-functional mediators in allergic rhinitis","volume":"36","author":"Gleason","year":"2006","journal-title":"Clin. Exp. Allergy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.prostaglandins.2008.11.002","article-title":"G2A as a receptor for oxidized free fatty acids","volume":"89","author":"Obinata","year":"2009","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/nature05877","article-title":"Resolvin E1 and protectin D1 activate inflammation-resolution programmes","volume":"447","author":"Schwab","year":"2007","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3383","DOI":"10.4049\/jimmunol.0900327","article-title":"12\/15-lipoxygenase counteracts inflammation and tissue damage in arthritis","volume":"183","author":"Kronke","year":"2009","journal-title":"J. Immunol."},{"key":"ref_17","first-page":"605101","article-title":"Anti-Inflammatory Effects of Epoxyeicosatrienoic Acids","volume":"2012","author":"Thomson","year":"2012","journal-title":"Int. J. Vasc. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"481","DOI":"10.4168\/aair.2016.8.6.481","article-title":"Eicosanoid Mediators in the Airway Inflammation of Asthmatic Patients: What is New?","volume":"8","author":"Sanak","year":"2016","journal-title":"Allergy, Asthma Immunol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.3389\/fimmu.2019.01699","article-title":"Activation of Resolution Pathways to Prevent and Fight Chronic Inflammation: Lessons From Asthma and Inflammatory Bowel Disease","volume":"10","author":"Barnig","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/nature11042","article-title":"Infection regulates pro-resolving mediators that lower antibiotic requirements","volume":"484","author":"Chiang","year":"2012","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"21599","DOI":"10.1074\/jbc.M109.003822","article-title":"Lipidomic Analysis of Dynamic Eicosanoid Responses during the Induction and Resolution of Lyme Arthritis*","volume":"284","author":"Blaho","year":"2009","journal-title":"J. Boil. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.3389\/fmicb.2019.01826","article-title":"Pseudomonas aeruginosa Lipoxygenase LoxA Contributes to Lung Infection by Altering the Host Immune Lipid Signaling","volume":"10","author":"Morello","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.cell.2013.02.027","article-title":"The Lipid Mediator Protectin D1 Inhibits Influenza Virus Replication and Improves Severe Influenza","volume":"153","author":"Morita","year":"2013","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Schultz, D., Methling, K., Rothe, M., Lalk, M., and KoInfekt Study Group (2019). Eicosanoid Profile of Influenza A Virus Infected Pigs. Metabolites, 9.","DOI":"10.3390\/metabo9070130"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1177\/1753425916684934","article-title":"Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection","volume":"23","author":"Salina","year":"2016","journal-title":"Innate Immun."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Krause, J., Geginat, G., and Tammer, I. (2015). Prostaglandin E2 from Candida albicans Stimulates the Growth of Staphylococcus aureus in Mixed Biofilms. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135404"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.3389\/fmicb.2018.02447","article-title":"PGE2 Augments Inflammasome Activation and M1 Polarization in Macrophages Infected With Salmonella Typhimurium and Yersinia enterocolitica","volume":"9","author":"Sheppe","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e00144-18","DOI":"10.1128\/IAI.00144-18","article-title":"Identification of Specific Components of the Eicosanoid Biosynthetic and Signaling Pathway Involved in Pathological Inflammation during Intra-abdominal Infection with Candida albicans and Staphylococcus aureus","volume":"86","author":"Ikeh","year":"2018","journal-title":"Infect. Immun."},{"key":"ref_29","first-page":"1413","article-title":"Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology","volume":"8","author":"Shambat","year":"2015","journal-title":"Dis. Model. Mech."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1128\/IAI.00488-12","article-title":"Pneumococcal Interactions with Epithelial Cells Are Crucial for Optimal Biofilm Formation and Colonization In Vitro and In Vivo","volume":"80","author":"Marks","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Blom, R.A.M., Erni, S.T., Krempask\u00e1, K., Schaerer, O., Van Dijk, R.M., Amacker, M., Moser, C., Hall, S.R.R., Von Garnier, C., and Blank, F. (2016). A Triple Co-Culture Model of the Human Respiratory Tract to Study Immune-Modulatory Effects of Liposomes and Virosomes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163539"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/mBio.00810-19","article-title":"Influenza \"Trains\" the Host for Enhanced Susceptibility to Secondary Bacterial Infection","volume":"10","author":"Shirey","year":"2019","journal-title":"mBio"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1089\/jir.2010.0049","article-title":"Postinfluenza Bacterial Pneumonia: Host Defenses Gone Awry","volume":"30","author":"Ballinger","year":"2010","journal-title":"J. Interf. Cytokine Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"40676","DOI":"10.1074\/jbc.M507787200","article-title":"Identification of 9-Hydroxyoctadecadienoic Acid and Other Oxidized Free Fatty Acids as Ligands of the G Protein-coupled Receptor G2A","volume":"280","author":"Obinata","year":"2005","journal-title":"J. Boil. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1165\/ajrcmb.12.3.7873191","article-title":"5-Hydroxyeicosatetraenoic acid (HETE)-induced neutrophil transcellular migration is dependent upon enantiomeric structure","volume":"12","author":"Bittleman","year":"1995","journal-title":"Am. J. Respir. Cell Mol. Boil."},{"key":"ref_36","first-page":"55","article-title":"Neutrophil-aggregating activity of monohydroxyeicosatetraenoic acids","volume":"104","author":"Thomas","year":"1981","journal-title":"Am. J. Pathol."},{"key":"ref_37","first-page":"587","article-title":"Leukotriene synthesis by epithelial cells","volume":"18","author":"Luo","year":"2003","journal-title":"Histol. Histopathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"262","DOI":"10.4161\/adip.24835","article-title":"A role for 5-lipoxygenase products in obesity-associated inflammation and insulin resistance","volume":"2","author":"Neels","year":"2013","journal-title":"Adipocyte"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3389\/fncel.2014.00436","article-title":"The 5-lipoxygenase pathway: Oxidative and inflammatory contributions to the Alzheimer\u2019s disease phenotype","volume":"8","author":"Joshi","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.atherosclerosis.2015.04.783","article-title":"Novel anti-inflammatory therapies for the treatment of atherosclerosis","volume":"240","author":"Khan","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_41","first-page":"107","article-title":"Staphylococcus aureus and influenza A virus stimulate human bronchoalveolar cells to release histamine and leukotrienes","volume":"27","author":"Clementsen","year":"1989","journal-title":"Inflamm. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0165-5728(95)00009-Q","article-title":"Eicosanoid production by rat cerebral endothelial cells: Stimulation by lipopolysaccharide, interleukin-1 and interleukin-6","volume":"59","year":"1995","journal-title":"J. Neuroimmunol."},{"key":"ref_43","first-page":"33","article-title":"Why is coinfection with influenza virus and bacteria so difficult to control?","volume":"19","author":"Cauley","year":"2015","journal-title":"Discov. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1086\/430954","article-title":"Influenza virus neuraminidase contributes to secondary bacterial pneumonia","volume":"192","author":"Peltola","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_45","first-page":"4627","article-title":"Control of COX-2 gene expression through peroxisome proliferator-activated receptor gamma in human cervical cancer cells","volume":"9","author":"Han","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/34178","article-title":"The peroxisome proliferator-activated receptor-\u03b3 is a negative regulator of macrophage activation","volume":"391","author":"Ricote","year":"1998","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s10571-017-0554-5","article-title":"Roles of Peroxisome Proliferator-Activated Receptor Gamma on Brain and Peripheral Inflammation","volume":"38","author":"Villapol","year":"2017","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"L293","DOI":"10.1152\/ajplung.00287.2014","article-title":"Airway epithelial cell ppargamma modulates cigarette smoke-induced chemokine expression and emphysema susceptibility in mice","volume":"309","author":"Solleti","year":"2015","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1254\/jphs.FP0040574","article-title":"Increased excretion of urinary 20-HETE in rats with cyclosporine-induced nephrotoxicity","volume":"97","author":"Seki","year":"2005","journal-title":"J. Pharmacol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Shambat, S.M., Haggar, A., Vandenesch, F., Lina, G., Van Wamel, W.J.B., Arakere, G., Svensson, M., and Norrby-Teglund, A. (2014). Levels of Alpha-Toxin Correlate with Distinct Phenotypic Response Profiles of Blood Mononuclear Cells and with agr Background of Community-Associated Staphylococcus aureus Isolates. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106107"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"31360","DOI":"10.1038\/srep31360","article-title":"A point mutation in agrc determines cytotoxic or colonizing properties associated with phenotypic variants of st22 mrsa strains","volume":"6","author":"Siemens","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1038\/nprot.2014.180","article-title":"Influenza a virus isolation, culture and identification","volume":"9","author":"Eisfeld","year":"2014","journal-title":"Nat. Protoc."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/10\/3\/113\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:07:51Z","timestamp":1760173671000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/10\/3\/113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,18]]},"references-count":52,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["metabo10030113"],"URL":"https:\/\/doi.org\/10.3390\/metabo10030113","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,18]]}}}