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J Infect Dis. 2002 Aug 1;186(3):341-50. Epub 2002 Jul 10.

Lethal synergism between influenza virus and Streptococcus pneumoniae: characterization of a mouse model and the role of platelet-activating factor receptor.

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1
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA. jon.mccullers@stjude.org

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.

PMID:
12134230
DOI:
10.1086/341462
[Indexed for MEDLINE]
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