title: Alarmin function of galectin-9 in murine respiratory tularemia.
abstract: Sepsis is a complex immune disorder that is characterized by systemic hyperinflammation. Alarmins, which are multifunctional endogenous factors, have been implicated in exacerbation of inflammation in many immune disorders including sepsis. Here we show that Galectin-9, a host endogenous β-galactoside binding lectin, functions as an alarmin capable of mediating inflammatory response during sepsis resulting from pulmonary infection with Francisella novicida, a Gram negative bacterial pathogen. Our results show that this galectin is upregulated and is likely released during tissue damage in the lungs of F. novicida infected septic mice. In vitro, purified recombinant galectin-9 exacerbated F. novicida-induced production of the inflammatory mediators by macrophages and neutrophils. Concomitantly, Galectin-9 deficient (Gal-9-/-) mice exhibited improved lung pathology, reduced cell death and reduced leukocyte infiltration, particularly neutrophils, in their lungs. This positively correlated with overall improved survival of F. novicida infected Gal-9-/- mice as compared to their wild-type counterparts. Collectively, these findings suggest that galectin-9 functions as a novel alarmin by augmenting the inflammatory response in sepsis development during pulmonary F. novicida infection.
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, United States of America.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Steichen
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, United States of America.
authors.forename: Tanner J
authors.initials: TJ
authors.lastname: Simonson
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, United States of America.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Salmon
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, United States of America.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Metzger
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, United States of America.
authors.forename: Bibhuti B
authors.initials: BB
authors.lastname: Mishra
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, United States of America.
authors.forename: Jyotika
authors.initials: J
authors.lastname: Sharma
mesh_terms: D000067531:Alarmins / Q000502:physiology; D000818:Animals; D001996:Bronchopneumonia / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D005260:Female; D005603:Francisella / Q000276:immunology; D037161:Galectins / Q000502:physiology*; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D014406:Tularemia / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
chemical_list: D000067531:Alarmins; D037161:Galectins; D018836:Inflammation Mediators; C508186:galectin 9, mouse