Article ; Online: Dysregulated macrophage-inflammatory protein-2 expression drives illness in bacterial superinfection of influenza.
Journal of immunology (Baltimore, Md. : 1950)
2010 Volume 184, Issue 4, Page(s) 2001–2013
Abstract: ... of bacterial superinfection of influenza. ... of mechanisms have been proposed by which influenza may predispose to superinfection with an unrelated or ... Influenza-infected hosts are vulnerable to secondary bacterial infection, however, and an ensuing ...
| Abstract | Influenza virus infection is a leading cause of death and disability throughout the world. Influenza-infected hosts are vulnerable to secondary bacterial infection, however, and an ensuing bacterial pneumonia is actually the predominant cause of influenza-attributed deaths during pandemics. A number of mechanisms have been proposed by which influenza may predispose to superinfection with an unrelated or heterologous pathogen, but the subsequent interaction between the host, virus, and bacteria remains an understudied area. In this study, we develop and examine a novel model of heterologous pulmonary infection in which an otherwise subclinical Bordetella parapertussis infection synergizes with an influenza virus infection to yield a life-threatening secondary pneumonia. Despite a profound pulmonary inflammatory response and unaltered viral clearance, bacterial clearance was significantly impaired in heterologously infected mice. No deficits were observed in pulmonary or systemic adaptive immune responses or the viability or function of infiltrating inflammatory cells to explain this phenomenon, and we provide evidence that the onset of severe pulmonary inflammation actually precedes the increased bacterial burden, suggesting that exacerbated inflammation is independent of bacterial burden. To that end, neutralization of the ELR(+) inflammatory chemokine MIP-2 (CXCL2/GRO-beta) attenuated the inflammation, weight loss, and clinical presentation of heterologously infected mice without impacting bacterial burden. These data suggest that pulmonary inflammation, rather than pathogen burden, is the key threat during bacterial superinfection of influenza and that selective chemokine antagonists may be a novel therapeutic intervention in cases of bacterial superinfection of influenza. |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| MeSH term(s) | Animals ; Bordetella Infections/immunology ; Bordetella Infections/pathology ; Bordetella Infections/therapy ; Bordetella parapertussis/immunology ; Cell Line ; Chemokine CXCL2/antagonists & inhibitors ; Chemokine CXCL2/biosynthesis ; Chemokine CXCL2/physiology ; Dogs ; Female ; Gene Expression Regulation, Bacterial/immunology ; Gene Expression Regulation, Viral/immunology ; Inflammation Mediators/antagonists & inhibitors ; Inflammation Mediators/metabolism ; Inflammation Mediators/physiology ; Influenza A Virus, H1N1 Subtype/immunology ; Mice ; Mice, Inbred C57BL ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/pathology ; Orthomyxoviridae Infections/therapy ; Pneumonia, Bacterial/immunology ; Pneumonia, Bacterial/pathology ; Pneumonia, Bacterial/virology ; Pneumonia, Viral/immunology ; Pneumonia, Viral/microbiology ; Pneumonia, Viral/pathology ; Receptors, Interleukin-8B/antagonists & inhibitors ; Superinfection/immunology ; Superinfection/microbiology ; Superinfection/virology | ||||||||||
| Chemical Substances | Chemokine CXCL2 ; Cxcl2 protein, mouse ; Inflammation Mediators ; Receptors, Interleukin-8B | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2010-02-15 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 3056-9 | ||||||||||
| ISSN | 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381 | ||||||||||
| ISSN (online) | 1550-6606 | ||||||||||
| ISSN | 0022-1767 ; 1048-3233 ; 1047-7381 | ||||||||||
| DOI | 10.4049/jimmunol.0903304 | ||||||||||
| Shelf mark |
|
||||||||||
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Ud II Zs.37: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
|||
| Zs.MG 28: Show issues |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.