| Sepsis induces early alterations in innate immunity that impact mortality to secondary infection. | |
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MedLine Citation:
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PMID: 21106855 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Matthew J Delano; Terri Thayer; Sonia Gabrilovich; Kindra M Kelly-Scumpia; Robert D Winfield; Philip O Scumpia; Alex G Cuenca; Elizabeth Warner; Shannon M Wallet; Mark A Wallet; Kerri A O'Malley; Reuben Ramphal; Michael Clare-Salzer; Philip A Efron; Clayton E Mathews; Lyle L Moldawer |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-11-24 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 186 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-21 Completed Date: 2011-01-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 195-202 Citation Subset: AIM; IM |
Affiliation:
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Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL 32610, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bacteremia / immunology*, mortality*, pathology Cecum Disease Models, Animal Genetic Predisposition to Disease Immunity, Innate* / genetics Ligation Listeriosis / immunology, mortality, pathology Mice Mice, Inbred C57BL Mice, Knockout Neutrophils / immunology, pathology Pneumonia, Bacterial / immunology, mortality, pathology Pseudomonas Infections / immunology, mortality, pathology Punctures Sepsis / immunology*, mortality*, pathology Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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DE-016509/DE/NIDCR NIH HHS; R01 GM-40586/GM/NIGMS NIH HHS; R01 GM-81923/GM/NIGMS NIH HHS; T32 AR-007603/AR/NIAMS NIH HHS; T32 CA-106493/CA/NCI NIH HHS; T32 GM-08431/GM/NIGMS NIH HHS |
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