title: Macrophage Galactose-Type Lectin-1 Deficiency Is Associated with Increased Neutrophilia and Hyperinflammation in Gram-Negative Pneumonia.
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.
authors.affiliation: Department of Basic Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Jondle
authors.affiliation: Department of Basic Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202.
authors.forename: Atul
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Basic Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202.
authors.forename: Tanner J
authors.initials: TJ
authors.lastname: Simonson
authors.affiliation: Department of Basic Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202.
authors.forename: Benjamin
authors.identifier: http://orcid.org/0000-0002-1940-9565
authors.initials: B
authors.lastname: Larson
authors.affiliation: Department of Basic Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202.
authors.forename: Bibhuti B
authors.initials: BB
authors.lastname: Mishra
authors.affiliation: Department of Basic Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202 jyotika.sharma@med.und.edu.
authors.forename: Jyotika
authors.initials: J
authors.lastname: Sharma
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001212:Asialoglycoproteins / Q000172:deficiency*; D004195:Disease Models, Animal; D065206:Extracellular Traps / Q000276:immunology; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D016905:Gram-Negative Bacterial Infections / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007711:Klebsiella pneumoniae; D037181:Lectins, C-Type / Q000172:deficiency*; D007964:Leukocytosis / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000473:pathology
chemical_list: D001212:Asialoglycoproteins; C064720:Clec10a protein, mouse; D018836:Inflammation Mediators; D037181:Lectins, C-Type; D008565:Membrane Proteins