Galectin-3 reduces the severity of pneumococcal pneumonia by augmenting neutrophil function.
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.
Farnworth
Sarah L
SL
Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Henderson
Neil C
NC
Mackinnon
Alison C
AC
Atkinson
Kirsten M
KM
Wilkinson
Tom
T
Dhaliwal
Kevin
K
Hayashi
Katsutoshi
K
Simpson
A John
AJ
Rossi
Adriano G
AG
Haslett
Christopher
C
Sethi
Tariq
T
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D005434:Flow Cytometry; D037502:Galectin 3 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D018375:Neutrophil Activation / Q000502:physiology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000276:immunology
D037502:Galectin 3