Toll-like receptor 2 mediates fatal immunopathology in mice during treatment of secondary pneumococcal pneumonia following influenza

Asa Karlström, Sarah M. Heston, Kelli L. Boyd, Elaine I. Tuomanen, Jonathan Mccullers

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Host inflammatory responses contribute to the significant immunopathology that occurs during treatment of secondary bacterial pneumonia following influenza. We undertook the present study to determine the mechanisms underlying disparate outcomes in a mouse model with β-lactam and macrolide antibiotics. Lysis of superinfecting bacteria by ampicillin caused an extensive influx of neutrophils into the lungs resulting in a consolidative pneumonia, necrotic lung damage, and significant mortality. This was mediated through Toll-like receptor (TLR) 2 and was independent of TLR4 and the Streptococcus pneumoniae cytotoxin pneumolysin. Treatment with azithromycin prevented neutrophil accumulation and rescued mice from subsequent mortality. This effect was independent of the antibacterial activity of this macrolide since dual therapy with ampicillin and azithromycin against an azithromycin-resistant strain also was able to cure secondary pneumonia. These data suggest that strategies for eliminating bacteria without lysis coupled with immunomodulation of inflammation should be pursued clinically.

Original languageEnglish (US)
Pages (from-to)1358-1366
Number of pages9
JournalJournal of Infectious Diseases
Volume204
Issue number9
DOIs
StatePublished - Nov 1 2011
Externally publishedYes

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Pneumococcal Pneumonia
Toll-Like Receptor 2
Azithromycin
Human Influenza
Macrolides
Ampicillin
Pneumonia
Neutrophils
Bacteria
Bacterial Pneumonia
Lactams
Lung
Immunomodulation
Mortality
Cytotoxins
Streptococcus pneumoniae
Therapeutics
Anti-Bacterial Agents
Inflammation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Toll-like receptor 2 mediates fatal immunopathology in mice during treatment of secondary pneumococcal pneumonia following influenza. / Karlström, Asa; Heston, Sarah M.; Boyd, Kelli L.; Tuomanen, Elaine I.; Mccullers, Jonathan.

In: Journal of Infectious Diseases, Vol. 204, No. 9, 01.11.2011, p. 1358-1366.

Research output: Contribution to journalArticle

Karlström, Asa ; Heston, Sarah M. ; Boyd, Kelli L. ; Tuomanen, Elaine I. ; Mccullers, Jonathan. / Toll-like receptor 2 mediates fatal immunopathology in mice during treatment of secondary pneumococcal pneumonia following influenza. In: Journal of Infectious Diseases. 2011 ; Vol. 204, No. 9. pp. 1358-1366.
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