Role of Galectin-3 in Leukocyte Recruitment in a Murine Model of Lung Infection by Streptococcus pneumoniae

Abstract

Pneumonia can be caused by a variety of pathogens, among which Streptococcus pneumoniae causes one of the most common forms of community-acquired pneumonia. Depending on the invading pathogen, the elements of the immune response triggered will vary. For most pathogens, such as Escherichia coli, neutrophil recruitment involves a well-described family of adhesion molecules, β2-integrins. In the case of streptococcal pneumonia, however, neutrophil recruitment occurs mainly through a β2-integrin-independent pathway. Despite decades of research on this issue, the adhesion molecules involved in neutrophil recruitment during lung infection by S. pneumoniae have not been identified. We have previously shown that galectin-3, a soluble mammalian lectin, can be found in lungs infected by S. pneumoniae, but not by E. coli, and can mediate the adhesion of neutrophils on the endothelial cell layer, implying its role in the recruitment of neutrophils to lungs infected with S. pneumoniae. In this study, using galectin-3 null mice, we report further evidence of the involvement of this soluble lectin in the recruitment of neutrophils to S. pneumonia-infected lungs. Indeed, in the absence of galectin-3, lower numbers of leukocytes, mainly neutrophils, were recruited to the infected lungs during infection by S. pneumoniae. In the case of β2-integrin-dependent recruitment induced by lung infection with E. coli, the number of recruited neutrophils was not reduced. Thus, taken together, our data suggest that galectin-3 plays a role as a soluble adhesion molecule in the recruitment of neutrophils to lungs infected by S. pneumoniae, which induces β2-integrin-independent migration.

Endogenous galectins and the control of the host inflammatory response

“…Gal-3 also promotes neutrophil adhesion to endothelial cells in vitro and may play an important role in beta-2 integrin-independent neutrophil extravasation in vivo (Sato et al 2002). These results, along with a decreased cellular infiltrate observed in numerous in vivo models of inflammation performed in Gal-3 null mice, provide evidence for a role for this galectin in mediating leukocyte recruitment during an inflammatory response (Colnot et al 1998a,b, Bernardes et al 2006, Nieminen et al 2008 With regards to apoptosis, Gal-3 appears to function differently in relation to its localisation, i.e. whether it is inside or outside the cell.…”

Lack of galectin‐3 alters the balance of innate immune cytokines and confers resistance to Rhodococcus equi infection

“…However, 5 days postinfection the intensity of the inflammatory response was even higher in the liver of gal3 À/À mice. Recently, Nieminen and colleagues reported [36] that the neutrophil recruitment was impaired in Streptococcus pneumoniae-infected gal3 À/À mice, whereas a larger number of neutrophils were detected in the BAL fluids of Escherichia coli-infected gal3 À/À mice, when compared with gal3 1/1 mice. In our study, the enhanced inflammatory response that occurred at later times postinfection did not corroborate the previously reported proinflammatory role of galectin-3 and may reflect a differential role of galectin-3 on the various cell types that compose the granuloma.…”

Galectin-3 Is Required for Resident Microglia Activation and Proliferation in Response to Ischemic Injury

“…Galectin-3 also modulates cytokine responses to pathogen (Rabinovich and Toscano, 2009). For innate immune cells, galectin-3 is suggested to be involved in neutrophil migration in streptococcal pneumonia (Sato et al, 2002;Nieminen et al, 2008). Once migrated, neutrophils are also activated by galectin-3, which results in degranulation of various layers of microbicidal factors (Yamaoka et al, 1995;Karlsson et al, 1998;Nieminen et al, 2005Nieminen et al, , 2007.…”