title: Sepsis induces early alterations in innate immunity that impact mortality to secondary infection.
abstract: Sepsis, the systemic inflammatory response to microbial infection, induces changes in both innate and adaptive immunity that presumably lead to increased susceptibility to secondary infections, multiorgan failure, and death. Using a model of murine polymicrobial sepsis whose severity approximates human sepsis, we examined outcomes and defined requirements for survival after secondary Pseudomonas aeruginosa pneumonia or disseminated Listeria monocytogenes infection. We demonstrate that early after sepsis neutrophil numbers and function are decreased, whereas monocyte recruitment through the CCR2/MCP-1 pathway and function are enhanced. Consequently, lethality to Pseudomonas pneumonia is increased early but not late after induction of sepsis. In contrast, lethality to listeriosis, whose eradication is dependent upon monocyte/macrophage phagocytosis, is actually decreased both early and late after sepsis. Adaptive immunity plays little role in these secondary infectious responses. This study demonstrates that sepsis promotes selective early, impaired innate immune responses, primarily in neutrophils, that lead to a pathogen-specific, increased susceptibility to secondary infections.
authors.affiliation: Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Delano
authors.forename: Terri
authors.initials: T
authors.lastname: Thayer
authors.forename: Sonia
authors.initials: S
authors.lastname: Gabrilovich
authors.forename: Kindra M
authors.initials: KM
authors.lastname: Kelly-Scumpia
authors.forename: Robert D
authors.initials: RD
authors.lastname: Winfield
authors.forename: Philip O
authors.initials: PO
authors.lastname: Scumpia
authors.forename: Alex G
authors.initials: AG
authors.lastname: Cuenca
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Warner
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Wallet
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wallet
authors.forename: Kerri A
authors.initials: KA
authors.lastname: O'Malley
authors.forename: Reuben
authors.initials: R
authors.lastname: Ramphal
authors.forename: Michael
authors.initials: M
authors.lastname: Clare-Salzer
authors.forename: Philip A
authors.initials: PA
authors.lastname: Efron
authors.forename: Clayton E
authors.initials: CE
authors.lastname: Mathews
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D002432:Cecum; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D008026:Ligation; D008088:Listeriosis / Q000276:immunology / Q000401:mortality / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000401:mortality / Q000473:pathology; D011552:Pseudomonas Infections / Q000276:immunology / Q000401:mortality / Q000473:pathology; D011677:Punctures; D018805:Sepsis / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D013997:Time Factors