Macrophage Galactose-Type Lectin-1 Deficiency Is Associated with Increased Neutrophilia and Hyperinflammation in Gram-Negative Pneumonia

J Immunol. 2016 Apr 1;196(7):3088-96. doi: 10.4049/jimmunol.1501790. Epub 2016 Feb 24.

Abstract

C-type lectin receptors (CLRs), the carbohydrate-recognizing molecules, orchestrate host immune response in homeostasis and in inflammation. In the present study we examined the function of macrophage galactose-type lectin-1 (MGL1), a mammalian CLR, in pneumonic sepsis, a deadly immune disorder frequently associated with a nonresolving hyperinflammation. In a murine model of pneumonic sepsis using pulmonary infection with Klebsiella pneumoniae, the expression of MGL1 was upregulated in the lungs of K. pneumoniae-infected mice, and the deficiency of this CLR in MGL1(-/-) mice resulted in significantly increased mortality to infection than in the MGL1-sufficient wild-type mice, despite a similar bacterial burden. The phagocytic cells from MGL1(-/-) mice did not exhibit any defects in bacterial uptake and intracellular killing and were fully competent in neutrophil extracellular trap formation, a recently identified extracellular killing modality of neutrophils. Instead, the increased susceptibility of MGL1(-/-) mice seemed to correlate with severe lung pathology, indicating that MGL1 is required for resolution of pulmonary inflammation. Indeed, the MGL1(-/-) mice exhibited a hyperinflammatory response, massive pulmonary neutrophilia, and an increase in neutrophil-associated immune mediators. Concomitantly, MGL1-deficient neutrophils exhibited an increased influx in pneumonic lungs of K. pneumoniae-infected mice. Taken together, these results show a previously undetermined role of MGL1 in controlling neutrophilia during pneumonic infection, thus playing an important role in resolution of inflammation. To our knowledge, this is the first study depicting a protective function of MGL1 in an acute pneumonic bacterial infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Asialoglycoproteins / deficiency*
  • Disease Models, Animal
  • Extracellular Traps / immunology
  • Gene Expression
  • Genetic Predisposition to Disease
  • Gram-Negative Bacterial Infections / genetics*
  • Gram-Negative Bacterial Infections / immunology*
  • Gram-Negative Bacterial Infections / microbiology
  • Gram-Negative Bacterial Infections / mortality
  • Gram-Negative Bacterial Infections / pathology
  • Inflammation Mediators / metabolism
  • Klebsiella pneumoniae
  • Lectins, C-Type / deficiency*
  • Leukocytosis / immunology
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Membrane Proteins / deficiency*
  • Mice
  • Mice, Knockout
  • Neutrophil Infiltration / genetics
  • Neutrophil Infiltration / immunology
  • Neutrophils / immunology*
  • Neutrophils / pathology
  • Phagocytosis / genetics
  • Phagocytosis / immunology
  • Pneumonia, Bacterial / genetics*
  • Pneumonia, Bacterial / immunology*
  • Pneumonia, Bacterial / microbiology
  • Pneumonia, Bacterial / mortality
  • Pneumonia, Bacterial / pathology

Substances

  • Asialoglycoproteins
  • Clec10a protein, mouse
  • Inflammation Mediators
  • Lectins, C-Type
  • Membrane Proteins