Galectin-3 reduces the severity of pneumococcal pneumonia by augmenting neutrophil function

Sarah Farnworth, Neil C. Henderson, Alison C. MacKinnon, Kirsten M. Atkinson, Tom Wilkinson, Kevin Dhaliwal, Katsutoshi Hayashi, A. John Simpson, Adriano G. Rossi, Christopher Haslett, Tariq Sethi

Research output: Contribution to journalArticlepeer-review

Abstract

The Gram-positive Streptococcus pneumoniae is the leading cause of community-acquired pneumonia worldwide, resulting in high mortality. Our in vivo studies show that galectin-3(-/-) mice develop more severe pneumonia after infection with S. pneumoniae, as demonstrated by increased bacteremia and lung damage compared to wild-type mice and that galectin-3 reduces the severity of pneumococcal pneumonia in part by augmenting neutrophil function. Specifically, we show that 1) galectin-3 directly acts as a neutrophil-activating agent and potentiates the effect of fMLP, 2) exogenous galectin-3 augments neutrophil phagocytosis of bacteria and delays neutrophil apoptosis, 3) phagocytosis of apoptotic neutrophils by galectin-3(-/-) macrophages is less efficient compared to wild type, and 4) galectin-3 demonstrates bacteriostatic properties against S. pneumoniae in vitro. Furthermore, ad-back of recombinant galectin-3 in vivo protects galectin-3-deficient mice from developing severe pneumonia. Together, these results demonstrate that galectin-3 is a key molecule in the host defense against pneumococcal infection. Therapeutic strategies designed to augment galectin-3 activity may both enhance inflammatory cell function (by directly affecting neutrophil responsiveness and prolonging neutrophil longevity) and have direct bacteriostatic activity, improving clinical outcomes after severe pneumococcal infection.

Original languageEnglish
Pages (from-to)395-405
Number of pages11
JournalAmerican Journal of Pathology
Volume172
Issue number2
DOIs
Publication statusPublished - Feb 2008

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