The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Lethal Synergism between Influenza Virus and Streptococcus pneumoniae: Characterization of a Mouse Model and the Role of Platelet‐Activating Factor Receptor
Abstract
A lethal synergism exists between influenza virus and pneumococcus, which likely accounts for excess mortality from secondary bacterial pneumonia during influenza epidemics. Characterization of a mouse model of synergy revealed that influenza infection preceding pneumococcal challenge primed for pneumonia and led to 100% mortality. This effect was specific for viral infection preceding bacterial infection, because reversal of the order of administration led to protection from influenza and improved survival. The hypothesis that influenza up-regulates the platelet-activating factor receptor (PAFr) and thereby potentiates pneumococcal adherence and invasion in the lung was examined in the model. Groups of mice receiving CV-6209, a competitive antagonist of PAFr, had survival rates similar to those of control mice, and lung and blood bacterial titers increased during PAFr inhibition. These data suggest that PAFr-independent pathways are operative in the model, prompting further study of receptor interactions during pneumonia and bacteremia. The model of lethal synergism will be a useful tool for exploring this and other mechanisms underlying viral-bacterial interactions.
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In the citing paper
“The timing of infection with the 2 organisms in coinfection models affects outcomes.”
From Influenza virus primes mice for pneumonia from Staphylococcus aureus. (2011) · cites this paper as [23]
In the citing paper
“In the pneumococcal secondary infection model, influenza virus enhances the bacterial load of S. pneumoniae recovered from the lungs and blood of mice, and strain-specific differences between outcomes are directly related to the total bacterial lung load [23,32,33].”
From Influenza virus primes mice for pneumonia from Staphylococcus aureus. (2011) · cites this paper as [23]
In the citing paper
“Little to no enhancement of disease is seen if the bacterial infection precedes exposure to the virus or the organisms are encountered together [23].”
From Influenza virus primes mice for pneumonia from Staphylococcus aureus. (2011) · cites this paper as [23]
In the citing paper
“Roughly 3-10 days after viral infection, a proinflammatory state characterized by granulocyte and monocyte influx into the lungs amplifies host responses to bacteria, resulting in poor outcomes [23,25,43].”
From Influenza virus primes mice for pneumonia from Staphylococcus aureus. (2011) · cites this paper as [23]
In the citing paper
“There seems to be biphasic response to the virus that alters innate responses to the secondary bacterial pathogen.”
From Influenza virus primes mice for pneumonia from Staphylococcus aureus. (2011) · cites this paper as [23]
Citations
Cites
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Streptococcus pneumoniae colonisation: the key to pneumococcal disease
Bogaert, D., de Groot, R., & Hermans, P. (2004) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(04)00938-7 · Cited by 1,929
Syndemics and public health: Reconceptualizing disease in bio-social context
Singer, M., & Clair, S. (2003) · Medical Anthropology Quarterly · doi:10.1525/maq.2003.17.4.423 · Cited by 1,140
Streptococcus pneumoniae: transmission, colonization and invasion
Weiser, J. N., Ferreira, D. M., & Paton, J. C. (2018) · Nature Reviews Microbiology · doi:10.1038/s41579-018-0001-8 · Cited by 1,152
Insights into the Interaction between Influenza Virus and Pneumococcus
McCullers, J. A. (2006) · Clinical Microbiology Reviews · doi:10.1128/cmr.00058-05 · Cited by 846
Self-citationThe co-pathogenesis of influenza viruses with bacteria in the lung.
McCullers, J. A. (2014) · Nature Reviews Microbiology · doi:10.1038/nrmicro3231 · Cited by 722
Self-citation
Metadata
- Authors
- McCullers, J. A., & Rehg, J. E.
- Affiliations
- St. Jude Children's Research Hospital (US)
- ORCID
- Rehg, Jerold E.
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-08
- Volume
- 186
- Issue
- 3
- Pages
- 341-350
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- OpenAlex
- W2105680176
- Cited by
- 423
- References
- 48
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 9 · 2023: 16 · 2022: 17 · 2021: 20 · 2020: 23 · 2019: 26 · 2018: 18 · 2017: 17 · 2016: 31 · 2015: 23 · 2014: 32 · 2013: 32 · 2012: 20
- FWCI
- 7.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1k08ai049178-01)
- National Cancer Institute (CA21765, P30CA021765)
- National Institute of Allergy and Infectious Diseases (AI-49178)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Keywords
- influenza virus, Streptococcus pneumoniae, secondary bacterial pneumonia, platelet-activating factor receptor, CV-6209, bacteremia, mouse model, host-pathogen interaction
- MeSH terms
- Animals, Disease Models, Animal, Female, Lung, Mice, Inbred BALB C, Orthomyxoviridae, Orthomyxoviridae Infections, Platelet Membrane Glycoproteins, Pneumonia, Pneumococcal, Pyridinium Compounds, Receptors, Cell Surface, Streptococcus pneumoniae, Receptors, G-Protein-Coupled, Mice
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