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This enhanced protection in obese mice was associated with early production of the lipid mediator prostaglandin D2 (PGD2), reduced prostaglandin E2 levels, attenuated pulmonary inflammation and decreased lung cell death. Using in vitro models, we found that PGD2 and its metabolites, PGJ2 and 15-deoxy-PGJ2, suppressed macrophage inflammatory responses and limited replication of both F. tularensis and B. pertussis. In studies using the highly virulent F. tularensis SchuS4 strain, antagonism of the PGD2 receptor DP2 increased bacterial burden in macrophages in vitro, and activation of both PGD2 receptors (DP1 and DP2) in lean mice reduced bacterial loads and lung inflammation in vivo. Together, these data indicate that PGD2 signaling promotes bacterial control and limits inflammation during these bacterial infections. The association between early PGD2 production and enhanced resistance to F. tularensis and B. pertussis in obese mice suggests that modulation of PGD2 signaling may contribute to obesity-associated protection and represents a potential host-directed therapeutic strategy to improve protection of these infections.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag254","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:08:13Z","timestamp":1790197693000},"source":"Crossref","is-referenced-by-count":0,"title":["Prostaglandin D2 production in obese mice is associated with reduced lung inflammation and improved control of\n                    <i>Francisella tularensis<\/i>\n                    and\n                    <i>Bordetella pertussis<\/i>\n                    infection"],"prefix":"10.1093","volume":"215","author":[{"given":"Monica A","family":"Valtierra-Alvarado","sequence":"first","affiliation":[{"name":"Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Hamilton, MT,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia M","family":"Roberts","sequence":"additional","affiliation":[{"name":"Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Hamilton, MT,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Forrest","family":"Jessop","sequence":"additional","affiliation":[{"name":"Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Hamilton, MT,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara 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